Pathogens

14 pages, 628 KiB

Open AccessEditor’s ChoiceReview

Gut Microbiome in Psoriasis: An Updated Review

by Mariusz Sikora, Albert Stec, Magdalena Chrabaszcz, Aleksandra Knot, Anna Waskiel-Burnat, Adriana Rakowska, Malgorzata Olszewska and Lidia Rudnicka

Pathogens 2020, 9(6), 463; https://doi.org/10.3390/pathogens9060463 - 12 Jun 2020

Cited by 56 | Viewed by 5797

Abstract

(1) Background: A growing body of evidence highlights that intestinal dysbiosis is associated with the development of psoriasis. The gut–skin axis is the novel concept of the interaction between skin diseases and microbiome through inflammatory mediators, metabolites and the intestinal barrier. The objective [...] Read more.

(1) Background: A growing body of evidence highlights that intestinal dysbiosis is associated with the development of psoriasis. The gut–skin axis is the novel concept of the interaction between skin diseases and microbiome through inflammatory mediators, metabolites and the intestinal barrier. The objective of this study was to synthesize current data on the gut microbial composition in psoriasis. (2) Methods: We conducted a systematic review of studies investigating intestinal microbiome in psoriasis, using the PRISMA checklist. We searched MEDLINE, EMBASE, and Web of Science databases for relevant published articles (2000–2020). (3) Results: All of the 10 retrieved studies reported alterations in the gut microbiome in patients with psoriasis. Eight studies assessed alpha- and beta-diversity. Four of them reported a lack of change in alpha-diversity, but all confirmed significant changes in beta-diversity. At the phylum-level, at least two or more studies reported a lower relative abundance of Bacteroidetes, and higher Firmicutes in psoriasis patients versus healthy controls. (4) Conclusions: There is a significant association between alterations in gut microbial composition and psoriasis; however, there is high heterogeneity between studies. More unified methodological standards in large-scale studies are needed to understand microbiota’s contribution to psoriasis pathogenesis and its modulation as a potential therapeutic strategy. Full article

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16 pages, 1865 KiB

Open AccessEditor’s ChoiceArticle

Physiological Responses to a Single Low-Dose of Bacillus anthracis Spores in the Rabbit Model of Inhalational Anthrax

by Sarah C. Taft, Tonya L. Nichols, Stephanie A. Hines, Roy E. Barnewall, Gregory V. Stark and Jason E. Comer

Pathogens 2020, 9(6), 461; https://doi.org/10.3390/pathogens9060461 - 11 Jun 2020

Cited by 1 | Viewed by 2413

Abstract

Credible dose–response relationships are needed to more accurately assess the risk posed by exposure to low-level Bacillus anthracis contamination during or following a release. To begin to fill this knowledge gap, New Zealand White rabbits were implanted with D70-PCT telemetry transmitters and subsequently [...] Read more.

Credible dose–response relationships are needed to more accurately assess the risk posed by exposure to low-level Bacillus anthracis contamination during or following a release. To begin to fill this knowledge gap, New Zealand White rabbits were implanted with D70-PCT telemetry transmitters and subsequently aerosol challenged with average inhaled doses of 2.86 × 10² to 2.75 × 10⁵ colony forming units (CFU) of B. anthracis spores. Rabbits exposed to a single inhaled dose at or above 2.54 × 10⁴ CFU succumbed with dose-dependent time to death. Death was associated with increases above baseline in heart rate, respiration rate, and body temperature and all rabbits that died exhibited bacteremia at some point prior to death. Rabbits that inhaled doses of 2.06 × 10³ CFU or lower survived to the end of the study and showed no or minimal adverse changes in the measured physiological responses in response to the challenge. Moreover, no bacteremia nor toxemia were observed in rabbits that survived to the end of the study. Overall, the data indicate that challenge doses of B. anthracis below the level sufficient to establish systemic infection do not produce observable physiological responses; however, doses that triggered a response resulted in death. Full article

(This article belongs to the Special Issue Anthrax Treatment)

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11 pages, 257 KiB

Open AccessEditor’s ChoiceArticle

Molecular Detection of Borrelia burgdorferi Sensu Lato and Anaplasma phagocytophilum in Ticks Collected from Dogs in Urban Areas of North-Eastern Poland

by Mirosław M. Michalski, Katarzyna Kubiak, Magdalena Szczotko, Marta Chajęcka and Małgorzata Dmitryjuk

Pathogens 2020, 9(6), 455; https://doi.org/10.3390/pathogens9060455 - 09 Jun 2020

Cited by 18 | Viewed by 2997

Abstract

From 2016 to 2018, ticks were collected from 272 dogs admitted to veterinary clinics in the city of Olsztyn (north-eastern Poland). Among 522 collected ticks, 423 were identified as Ixodes ricinus (413 females and 10 males) and 99 as Dermacentor reticulatus (62 females [...] Read more.

From 2016 to 2018, ticks were collected from 272 dogs admitted to veterinary clinics in the city of Olsztyn (north-eastern Poland). Among 522 collected ticks, 423 were identified as Ixodes ricinus (413 females and 10 males) and 99 as Dermacentor reticulatus (62 females and 37 males). Non-engorged (86 individuals) and engorged (436 individuals) ticks were screened for the presence of Borrelia burgdorferi sensu lato and Anaplasma phagocytophilum DNA. Borrelia and A. phagocytophilum species detection was determined based on the sequence of the fla B and 16S RNA genes, respectively. DNA of B. burgdorferi s.l. was identified in 31.6% (165/522, 95% CI: 27.6–35.8%) of ticks (I. ricinus 151/423, 35.7%, 95% CI: 31.1–40.4%; D. reticulates 14/99, 14.1%, 95% CI: 7.9–22.6%). A. phagocytophilum was identified in 0.96% (5/522, 95% CI: 0.3–2.2%) of specimens. All positive samples were engorged I. ricinus females (5/402, 1.2%, 95% CI: 0.4–2.9%). In 85.4% (141/165, 95% CI: 79.1–90.4%) of Borrelia infected ticks, the DNA of one genospecies was revealed. The DNA of at least two different genospecies was detected in 14.5% of specimens (24/165, 95% CI: 9.5–20.8). The coexistence of B. burgdorferii s.l. and A. phagocytophilum was not detected. Full article

9 pages, 209 KiB

Open AccessEditor’s ChoiceReview

The Molecular Epidemiology of Echinococcus Infections

by R. C. Andrew Thompson

Pathogens 2020, 9(6), 453; https://doi.org/10.3390/pathogens9060453 - 08 Jun 2020

Cited by 25 | Viewed by 3996

Abstract

Molecular epidemiology (ME) is the application of molecular tools to determine the causation of disease. With infectious diseases, such as echinococcosis, this applies to identifying and characterising the aetiological agents and elucidating host range. Such an approach has been very successful with the [...] Read more.

Molecular epidemiology (ME) is the application of molecular tools to determine the causation of disease. With infectious diseases, such as echinococcosis, this applies to identifying and characterising the aetiological agents and elucidating host range. Such an approach has been very successful with the causative agents of echinococcosis, species of Echinococcus, initially by providing a workable and practical taxonomy and subsequently determining transmission patterns in endemic areas. This review summarises the taxonomy and nomenclature of species of Echinococcus and provides an update on ME investigations of the ecology of Echinococcus transmission, particularly in areas where more than one species of Echinococcus is maintained in cycles of transmission that may interact. Full article

(This article belongs to the Special Issue Echinococcus)

15 pages, 605 KiB

Open AccessEditor’s ChoiceArticle

Group A Rotavirus Detection and Genotype Distribution before and after Introduction of a National Immunisation Programme in Ireland: 2015–2019

by Zoe Yandle, Suzie Coughlan, Jonathan Dean, Gráinne Tuite, Anne Conroy and Cillian F. De Gascun

Pathogens 2020, 9(6), 449; https://doi.org/10.3390/pathogens9060449 - 07 Jun 2020

Cited by 14 | Viewed by 3075

Abstract

Immunisation against rotavirus infection was introduced into Ireland in December 2016. We report on the viruses causing gastroenteritis before (2015–2016) and after (2017–2019) implementation of the Rotarix vaccine, as well as changes in the diversity of circulating rotavirus genotypes. Samples from patients aged [...] Read more.

Immunisation against rotavirus infection was introduced into Ireland in December 2016. We report on the viruses causing gastroenteritis before (2015–2016) and after (2017–2019) implementation of the Rotarix vaccine, as well as changes in the diversity of circulating rotavirus genotypes. Samples from patients aged ≤ 5 years (n = 11,800) were received at the National Virus Reference Laboratory, Dublin, and tested by real-time RT-PCR for rotavirus, Rotarix, norovirus, sapovirus, astrovirus, and enteric adenovirus. Rotavirus genotyping was performed either by multiplex or hemi-nested RT-PCR, and a subset was characterised by sequence analysis. Rotavirus detection decreased by 91% in children aged 0–12 months between 2015/16 and 2018/19. Rotarix was detected in 10% of those eligible for the vaccine and was not found in those aged >7 months. Rotavirus typically peaks in March–May, but following vaccination, the seasonality became less defined. In 2015–16, G1P[8] was the most common genotype circulating; however, in 2019 G2P[4] was detected more often. Following the introduction of Rotarix, a reduction in numbers of rotavirus infections occurred, coinciding with an increase in genotype diversity, along with the first recorded detection of an equine-like G3 strain in Ireland. Full article

(This article belongs to the Special Issue Rotaviruses and Rotavirus Vaccines)

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8 pages, 401 KiB

Open AccessEditor’s ChoiceArticle

A Targeted “Next-Generation” Sequencing-Informatic Approach to Define Genetic Diversity in Theileria orientalis Populations within Individual Cattle: Proof-of-Principle

by Anson V. Koehler, Abdul Jabbar, Ross S. Hall and Robin B. Gasser

Pathogens 2020, 9(6), 448; https://doi.org/10.3390/pathogens9060448 - 05 Jun 2020

Cited by 4 | Viewed by 2442

Abstract

Oriental theileriosis is an economically important tickborne disease of bovines, caused by some members of the Theileria orientalis complex. Currently, 11 distinct operational taxonomic units (OTUs), or genotypes, are recognized based on their major piroplasm surface protein (MPSP) gene sequences. Two [...] Read more.

Oriental theileriosis is an economically important tickborne disease of bovines, caused by some members of the Theileria orientalis complex. Currently, 11 distinct operational taxonomic units (OTUs), or genotypes, are recognized based on their major piroplasm surface protein (MPSP) gene sequences. Two of these genotypes (i.e., chitose and ikeda) are recognized as pathogenic in cattle, causing significant disease in countries of the Asia-Pacific region. However, the true extent of genetic variation and associated virulence/pathogenicity within this complex is unknown. Here, we undertook a proof-of-principle study of a small panel of genomic DNAs (n = 13) from blood samples originating from individual cattle known to harbor T. orientalis, in order to assess the performance of a targeted “next-generation” sequencing-informatic approach to identify genotypes. Five genotypes (chitose, ikeda, buffeli, type 4, and type 5) were defined; multiple genotypes were found within individual samples, with dominant and minor sequence types representing most genotypes. This study indicates that this sequencing-informatic workflow could be useful to assess the nature and extent of genetic variation within and among populations of T. orientalis on a large scale, and to potentially employ panels of distinct gene markers for expanded molecular epidemiological investigations of socioeconomically important protistan pathogens more generally. Full article

(This article belongs to the Special Issue Animal Parasitic Diseases)

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17 pages, 1664 KiB

Open AccessEditor’s ChoiceReview

Parasite Cystatin: Immunomodulatory Molecule with Therapeutic Activity against Immune Mediated Disorders

by Vishal Khatri, Nikhil Chauhan and Ramaswamy Kalyanasundaram

Pathogens 2020, 9(6), 431; https://doi.org/10.3390/pathogens9060431 - 30 May 2020

Cited by 16 | Viewed by 3541

Abstract

The use of parasites or their products for treating chronic inflammation associated diseases (CIADs) has generated significant attention recently. Findings from basic and clinical research have provided valuable information on strengthening the notion that parasites’ molecules can be developed as biotherapeutic agents. Completion [...] Read more.

The use of parasites or their products for treating chronic inflammation associated diseases (CIADs) has generated significant attention recently. Findings from basic and clinical research have provided valuable information on strengthening the notion that parasites’ molecules can be developed as biotherapeutic agents. Completion of the genome, secreotome, and proteome of the parasites has provided an excellent platform for screening and identifying several host immunomodulatory molecules from the parasites and evaluate their therapeutic potential for CIADs. One of the widely studied host immunomodulatory molecules of the parasites is the cysteine protease inhibitor (cystatin), which is primarily secreted by the parasites to evade host immune responses. In this review, we have attempted to summarize the findings to date on the use of helminth parasite-derived cystatin as a therapeutic agent against CIADs. Although several studies suggest a role for alternatively activated macrophages, other regulatory cells, and immunosuppressive molecules, in this immunoregulatory activity of the parasite-derived cystatin, there is still no clear demonstration as to how cystatin induces its anti-inflammatory effect in suppressing CIADs. Full article

(This article belongs to the Section Vaccines and Therapeutic Developments)

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22 pages, 1089 KiB

Open AccessEditor’s ChoiceReview

A Review on SARS-CoV-2 Virology, Pathophysiology, Animal Models, and Anti-Viral Interventions

by Sabari Nath Neerukonda and Upendra Katneni

Pathogens 2020, 9(6), 426; https://doi.org/10.3390/pathogens9060426 - 29 May 2020

Cited by 44 | Viewed by 9425

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of CoV disease 2019 (COVID-19) is a highly pathogenic and transmissible CoV that is presently plaguing the global human population and economy. No proven effective antiviral therapy or vaccine currently exists, and supportive [...] Read more.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of CoV disease 2019 (COVID-19) is a highly pathogenic and transmissible CoV that is presently plaguing the global human population and economy. No proven effective antiviral therapy or vaccine currently exists, and supportive care remains to be the cornerstone treatment. Through previous lessons learned from SARS-CoV-1 and MERS-CoV studies, scientific groups worldwide have rapidly expanded the knowledge pertaining to SARS-CoV-2 virology that includes in vitro and in vivo models for testing of antiviral therapies and randomized clinical trials. In the present narrative, we review SARS-CoV-2 virology, clinical features, pathophysiology, and animal models with a specific focus on the antiviral and adjunctive therapies currently being tested or that require testing in animal models and randomized clinical trials. Full article

(This article belongs to the Collection SARS-CoV Infections)

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15 pages, 1396 KiB

Open AccessEditor’s ChoiceArticle

Laboratory Diagnosis of Bovine Abortions Caused by Non-Maintenance Pathogenic Leptospira spp.: Necropsy, Serology and Molecular Study Out of a Belgian Experience

by Fabien Grégoire, Raïssa Bakinahe, Thierry Petitjean, Samira Boarbi, Laurent Delooz, David Fretin, Marc Saulmont and Marcella Mori

Pathogens 2020, 9(6), 413; https://doi.org/10.3390/pathogens9060413 - 26 May 2020

Cited by 11 | Viewed by 2916

Abstract

Bovine leptospirosis is a bacterial zoonotic disease caused by pathogenic Leptospira spp. The pathology and epidemiology of this infection are influenced by the numerous existing serovars and their adaptation to specific hosts. Infections by host-maintained serovars such as Hardjo are well documented, unlike [...] Read more.

Bovine leptospirosis is a bacterial zoonotic disease caused by pathogenic Leptospira spp. The pathology and epidemiology of this infection are influenced by the numerous existing serovars and their adaptation to specific hosts. Infections by host-maintained serovars such as Hardjo are well documented, unlike those from the incidental ones. In July 2014, an emerging phenomenon of an increased incidence of icteric abortions associated with leptospiral infection occurred in southern Belgium. First-line serological analyses targeting cattle-adapted serovars failed at initial diagnosis. This study provides a comprehensive description of laboratory findings—at the level of necropsy, serology and molecular diagnosis—regarding icteric and non-icteric abortions (n = 116) recorded during this time (years 2014–2015) and associated with incidental infection by serovars such as Grippotyphosa, Australis and Icterohaemorrhagiae. Based on these tests, a diagnostic pathway is proposed for these types of infection in cattle to establish an affordable but accurate diagnosis in the future. These investigations add insights into the understanding of the pathogenesis of bovine leptospirosis associated with serovars classically described as non-maintenance. Full article

(This article belongs to the Special Issue Leptospira infections in Domestic and Wild Animal)

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11 pages, 1896 KiB

Open AccessEditor’s ChoiceArticle

Analysis of the Leukocyte Response in Calves Suffered from Mycoplasma bovis Pneumonia

by Katarzyna Dudek, Dariusz Bednarek, Urszula Lisiecka, Anna Kycko, Michał Reichert, Krzysztof Kostro and Stanisław Winiarczyk

Pathogens 2020, 9(5), 407; https://doi.org/10.3390/pathogens9050407 - 24 May 2020

Cited by 10 | Viewed by 2810

Abstract

Mycoplasma bovis is known to be a cause of chronic pneumonia in cattle. To date, the disease pathomechanism has not been fully elucidated. Leukocytes play a key role in host antimicrobial defense mechanisms. Many in vitro studies of the effect of Mycoplasma bovis [...] Read more.

Mycoplasma bovis is known to be a cause of chronic pneumonia in cattle. To date, the disease pathomechanism has not been fully elucidated. Leukocytes play a key role in host antimicrobial defense mechanisms. Many in vitro studies of the effect of Mycoplasma bovis (M. bovis) on leukocytes have been performed, but it is difficult to apply these results to in vivo conditions. Additionally, only a few studies on a local immune response in M. bovis pneumonia have been undertaken. In this study, the experimental calf-infection model was used to determine the effect of field M. bovis strains on changes of the peripheral blood leukocyte response, including phagocytic activity and oxygen metabolism by cytometry analyses. An additional aim was to evaluate the lung local immunity of the experimentally infected calves using immunohistochemical staining. The general stimulation of phagocytic and killing activity of peripheral blood leukocytes in response to the M. bovis infection points to upregulation of cellular antimicrobial mechanisms. The local immune response in the infected lungs was characterized by the T- and B-cell stimulation, however, most seen in the increased T lymphocyte response. Post-infection, strong expression of the antigen-presenting cells and phagocytes also confirmed the activation of lung local immunity. In this study—despite the stimulation—both the peripheral and local cellular antimicrobial mechanisms seem to appear ineffective in eliminating M. bovis from the host and preventing the specific lung lesions, indicating an ability of the pathogen to avoid the host immune response in the M. bovis pneumonia. Full article

(This article belongs to the Special Issue Mycoplasma bovis Infections: Occurrence, Pathogenesis, Diagnosis and Control, Including Prevention and Therapy)

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9 pages, 228 KiB

Open AccessEditor’s ChoiceReview

Role of Hydrogen Peroxide Vapor (HPV) for the Disinfection of Hospital Surfaces Contaminated by Multiresistant Bacteria

by Michele Totaro, Beatrice Casini, Sara Profeti, Benedetta Tuvo, Gaetano Privitera and Angelo Baggiani

Pathogens 2020, 9(5), 408; https://doi.org/10.3390/pathogens9050408 - 24 May 2020

Cited by 19 | Viewed by 5643

Abstract

The emergence of multiresistant bacterial strains as agents of healthcare-related infection in hospitals has prompted a review of the control techniques, with an added emphasis on preventive measures, namely good clinical practices, antimicrobial stewardship, and appropriate environmental cleaning. The latter item is about [...] Read more.

The emergence of multiresistant bacterial strains as agents of healthcare-related infection in hospitals has prompted a review of the control techniques, with an added emphasis on preventive measures, namely good clinical practices, antimicrobial stewardship, and appropriate environmental cleaning. The latter item is about the choice of an appropriate disinfectant as a critical role due to the difficulties often encountered in obtaining a complete eradication of environmental contaminations and reservoirs of pathogens. The present review is focused on the effectiveness of hydrogen peroxide vapor, among the new environmental disinfectants that have been adopted. The method is based on a critical review of the available literature on this topic Full article

(This article belongs to the Section Waterborne/Foodborne/Airborne Pathogens)

14 pages, 3625 KiB

Open AccessEditor’s ChoiceArticle

A Conserved Tryptophan in the Ebola Virus Matrix Protein C-Terminal Domain Is Required for Efficient Virus-Like Particle Formation

by Kristen A. Johnson, Rudramani Pokhrel, Melissa R. Budicini, Bernard S. Gerstman, Prem P. Chapagain and Robert V. Stahelin

Pathogens 2020, 9(5), 402; https://doi.org/10.3390/pathogens9050402 - 22 May 2020

Cited by 7 | Viewed by 3320

Abstract

The Ebola virus (EBOV) harbors seven genes, one of which is the matrix protein eVP40, a peripheral protein that is sufficient to induce the formation of virus-like particles from the host cell plasma membrane. eVP40 can form different structures to fulfil different functions [...] Read more.

The Ebola virus (EBOV) harbors seven genes, one of which is the matrix protein eVP40, a peripheral protein that is sufficient to induce the formation of virus-like particles from the host cell plasma membrane. eVP40 can form different structures to fulfil different functions during the viral life cycle, although the structural dynamics of eVP40 that warrant dimer, hexamer, and octamer formation are still poorly understood. eVP40 has two conserved Trp residues at positions 95 and 191. The role of Trp⁹⁵ has been characterized in depth as it serves as an important residue in eVP40 oligomer formation. To gain insight into the functional role of Trp¹⁹¹ in eVP40, we prepared mutations of Trp¹⁹¹ (W191A or W191F) to determine the effects of mutation on eVP40 plasma membrane localization and budding as well as eVP40 oligomerization. These in vitro and cellular experiments were complemented by molecular dynamics simulations of the wild-type (WT) eVP40 structure versus that of W191A. Taken together, Trp is shown to be a critical amino acid at position 191 as mutation to Ala reduces the ability of VP40 to localize to the plasma membrane inner leaflet and form new virus-like particles. Further, mutation of Trp¹⁹¹ to Ala or Phe shifted the in vitro equilibrium to the octamer form by destabilizing Trp¹⁹¹ interactions with nearby residues. This study has shed new light on the importance of interdomain interactions in stability of the eVP40 structure and the critical nature of timing of eVP40 oligomerization for plasma membrane localization and viral budding. Full article

(This article belongs to the Section Viral Pathogens)

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14 pages, 1351 KiB

Open AccessEditor’s ChoiceReview

A Review: Wolbachia-Based Population Replacement for Mosquito Control Shares Common Points with Genetically Modified Control Approaches

by Pei-Shi Yen and Anna-Bella Failloux

Pathogens 2020, 9(5), 404; https://doi.org/10.3390/pathogens9050404 - 22 May 2020

Cited by 46 | Viewed by 8654

Abstract

The growing expansion of mosquito vectors has made mosquito-borne arboviral diseases a global threat to public health, and the lack of licensed vaccines and treatments highlight the urgent need for efficient mosquito vector control. Compared to genetically modified control strategies, the intracellular bacterium [...] Read more.

The growing expansion of mosquito vectors has made mosquito-borne arboviral diseases a global threat to public health, and the lack of licensed vaccines and treatments highlight the urgent need for efficient mosquito vector control. Compared to genetically modified control strategies, the intracellular bacterium Wolbachia, endowing a pathogen-blocking phenotype, is considered an environmentally friendly strategy to replace the target population for controlling arboviral diseases. However, the incomplete knowledge regarding the pathogen-blocking mechanism weakens the reliability of a Wolbachia-based population replacement strategy. Wolbachia infections are also vulnerable to environmental factors, temperature, and host diet, affecting their densities in mosquitoes and thus the virus-blocking phenotype. Here, we review the properties of the Wolbachia strategy as an approach to control mosquito populations in comparison with genetically modified control methods. Both strategies tend to limit arbovirus infections but increase the risk of selecting arbovirus escape mutants, rendering these strategies less reliable. Full article

(This article belongs to the Special Issue Untargeted Alternative Routes of Arbovirus Transmission)

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16 pages, 2368 KiB

Open AccessEditor’s ChoiceReview

The Relationship between Estrogen-Related Signaling and Human Papillomavirus Positive Cancers

by Claire D. James, Iain M. Morgan and Molly L. Bristol

Pathogens 2020, 9(5), 403; https://doi.org/10.3390/pathogens9050403 - 22 May 2020

Cited by 23 | Viewed by 6485

Abstract

High risk-human papillomaviruses (HPVs) are known carcinogens. Numerous reports have linked the steroid hormone estrogen, and the expression of estrogen receptors (ERs), to HPV-related cancers, although the exact nature of the interactions remains to be fully elucidated. Here we will focus on estrogen [...] Read more.

High risk-human papillomaviruses (HPVs) are known carcinogens. Numerous reports have linked the steroid hormone estrogen, and the expression of estrogen receptors (ERs), to HPV-related cancers, although the exact nature of the interactions remains to be fully elucidated. Here we will focus on estrogen signaling and describe both pro and potentially anti-cancer effects of this hormone in HPV-positive cancers. This review will summarize: (1) cell culture-related evidence, (2) animal model evidence, and (3) clinical evidence demonstrating an interaction between estrogen and HPV-positive cancers. This comprehensive review provides insights into the potential relationship between estrogen and HPV. We suggest that estrogen may provide a potential therapeutic for HPV-related cancers, however additional studies are necessary. Full article

(This article belongs to the Special Issue Viral-host interactions and determinants of human papillomavirus (HPV) life cycle and pathogenesis)

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23 pages, 1193 KiB

Open AccessEditor’s ChoiceReview

Vaccinia Virus as a Master of Host Shutoff Induction: Targeting Processes of the Central Dogma and Beyond

by Pragyesh Dhungel, Fernando M. Cantu, Joshua A. Molina and Zhilong Yang

Pathogens 2020, 9(5), 400; https://doi.org/10.3390/pathogens9050400 - 21 May 2020

Cited by 14 | Viewed by 7809

Abstract

The synthesis of host cell proteins is adversely inhibited in many virus infections, whereas viral proteins are efficiently synthesized. This phenomenon leads to the accumulation of viral proteins concurrently with a profound decline in global host protein synthesis, a phenomenon often termed “host [...] Read more.

The synthesis of host cell proteins is adversely inhibited in many virus infections, whereas viral proteins are efficiently synthesized. This phenomenon leads to the accumulation of viral proteins concurrently with a profound decline in global host protein synthesis, a phenomenon often termed “host shutoff”. To induce host shutoff, a virus may target various steps of gene expression, as well as pre- and post-gene expression processes. During infection, vaccinia virus (VACV), the prototype poxvirus, targets all major processes of the central dogma of genetics, as well as pre-transcription and post-translation steps to hinder host cell protein production. In this article, we review the strategies used by VACV to induce host shutoff in the context of strategies employed by other viruses. We elaborate on how VACV induces host shutoff by targeting host cell DNA synthesis, RNA production and processing, mRNA translation, and protein degradation. We emphasize the topics on VACV’s approaches toward modulating mRNA processing, stability, and translation during infection. Finally, we propose avenues for future investigations, which will facilitate our understanding of poxvirus biology, as well as fundamental cellular gene expression and regulation mechanisms. Full article

(This article belongs to the Special Issue Poxviruses: Novel Concepts and Emerging Trends)

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11 pages, 288 KiB

Open AccessEditor’s ChoiceArticle

Multiple Tick-Borne Pathogens in Ixodes ricinus Ticks Collected from Humans in Romania

by Zsuzsa Kalmár, Mirabela Oana Dumitrache, Gianluca D’Amico, Ioana Adriana Matei, Angela Monica Ionică, Călin Mircea Gherman, Mihaela Lupșe and Andrei Daniel Mihalca

Pathogens 2020, 9(5), 390; https://doi.org/10.3390/pathogens9050390 - 19 May 2020

Cited by 12 | Viewed by 3340

Abstract

Ticks are medically important vectors of infectious diseases that are able to transmit pathogens to humans and animals. Tick-borne diseases represent a major health concern, posing an increasing risk to the public health during the last century and affecting millions of people. The [...] Read more.

Ticks are medically important vectors of infectious diseases that are able to transmit pathogens to humans and animals. Tick-borne diseases represent a major health concern, posing an increasing risk to the public health during the last century and affecting millions of people. The aim of the current study was to provide epidemiological data regarding the presence of certain tick-borne pathogens in ticks feeding on humans in Romania. Overall, 522 Ixodes ricinus ticks collected from humans were screened for six pathogens: Borrelia spp., Neoehrlichia mikurensis, Babesia spp., Coxiella spp., Bartonella spp., and Francisella tularensis. Ticks attached to humans were collected between 2013–2015 in Cluj County, Romania. Conventional, nested and quantitative PCR were used to detect specific genetic sequences of each pathogen. For identifying the infectious agents, positive samples were sequenced. The infection prevalence was 21.07% from which 8.18% were mixed infections. The detected agents were Borrelia spp., N. mikurensis and Babesia spp. The present data reveal the endemic occurrence of potentially zoonotic pathogens in Romania. Revealing the current distribution of tick-borne pathogens in ticks collected from humans may provide new insights in understanding the complex ecology of tick-borne diseases and enlightens current knowledge about the infection prevalence at local, regional and national levels. Full article

13 pages, 764 KiB

Open AccessEditor’s ChoiceReview

The COVID-19 Pandemic during the Time of the Diabetes Pandemic: Likely Fraternal Twins?

by Shelley A. Cole, Hugo A. Laviada-Molina, Jeannette M. Serres-Perales, Ernesto Rodriguez-Ayala and Raul A. Bastarrachea

Pathogens 2020, 9(5), 389; https://doi.org/10.3390/pathogens9050389 - 19 May 2020

Cited by 13 | Viewed by 7919

Abstract

An altered immune response to pathogens has been suggested to explain increased susceptibility to infectious diseases in patients with diabetes. Recent evidence has documented several immunometabolic pathways in patients with diabetes directly related to the COVID-19 infection. This also seems to be the [...] Read more.

An altered immune response to pathogens has been suggested to explain increased susceptibility to infectious diseases in patients with diabetes. Recent evidence has documented several immunometabolic pathways in patients with diabetes directly related to the COVID-19 infection. This also seems to be the case for prediabetic subjects with proinflammatory insulin resistance syndrome accompanied with prothrombotic hyperinsulinemic and dysglycemic states. Patients with frank hyperglycemia, dysglycemia and/or hyperinsulinemia develop systemic immunometabolic inflammation with higher levels of circulating cytokines. This deleterious scenario has been proposed as the underlying mechanism enhancing a cytokine storm-like hyperinflammatory state in diabetics infected with severe COVID-19 triggering multi-organ failure. Compared with moderately affected COVID-19 patients, diabetes was found to be highly prevalent among severely affected patients suggesting that this non-communicable disease should be considered as a risk factor for adverse outcomes. The COVID-19 pandemic mirrors with the diabetes pandemic in many pathobiological aspects. Our interest is to emphasize the ties between the immunoinflammatory mechanisms that underlie the morbidity and lethality when COVID-19 meets diabetes. This review brings attention to two pathologies of highly complex, multifactorial, developmental and environmentally dependent manifestations of critical importance to human survival. Extreme caution should be taken with diabetics with suspected symptoms of COVID-19 infection. Full article

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18 pages, 1820 KiB

Open AccessEditor’s ChoiceArticle

Toll-Like Receptor-4 Dependent Intestinal and Systemic Sequelae Following Peroral Campylobacter coli Infection of IL10 Deficient Mice Harboring a Human Gut Microbiota

by Sigri Kløve, Claudia Genger, Soraya Mousavi, Dennis Weschka, Stefan Bereswill and Markus M. Heimesaat

Pathogens 2020, 9(5), 386; https://doi.org/10.3390/pathogens9050386 - 18 May 2020

Cited by 12 | Viewed by 3063

Abstract

Zoonotic Campylobacter, including C. jejuni and C. coli, are among the most prevalent agents of food-borne enteritis worldwide. The immunopathological sequelae of campylobacteriosis are caused by Toll-like Receptor-4 (TLR4)-dependent host immune responses, induced by bacterial lipooligosaccharide (LOS). In order to investigate [...] Read more.

Zoonotic Campylobacter, including C. jejuni and C. coli, are among the most prevalent agents of food-borne enteritis worldwide. The immunopathological sequelae of campylobacteriosis are caused by Toll-like Receptor-4 (TLR4)-dependent host immune responses, induced by bacterial lipooligosaccharide (LOS). In order to investigate C. coli-host interactions, including the roles of the human gut microbiota and TLR4, upon infection, we applied a clinical acute campylobacteriosis model, and subjected secondary abiotic, TLR4-deficient IL10^-/- mice and IL10^-/- controls to fecal microbiota transplantation derived from human donors by gavage, before peroral C. coli challenge. Until day 21 post-infection, C. coli could stably colonize the gastrointestinal tract of human microbiota-associated (hma) mice of either genotype. TLR4-deficient IL10^-/- mice, however, displayed less severe clinical signs of infection, that were accompanied by less distinct apoptotic epithelial cell and innate as well as adaptive immune cell responses in the colon, as compared to IL10^-/- counterparts. Furthermore, C. coli infected IL10^-/-, as opposed to TLR4-deficient IL10^-/-, mice displayed increased pro-inflammatory cytokine concentrations in intestinal and, strikingly, systemic compartments. We conclude that pathogenic LOS might play an important role in inducing TLR4-dependent host immune responses upon C. coli infection, which needs to be further addressed in more detail. Full article

(This article belongs to the Special Issue Campylobacter Infections)

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19 pages, 5491 KiB

Open AccessEditor’s ChoiceArticle

Neospora caninum: Structure and Fate of Multinucleated Complexes Induced by the Bumped Kinase Inhibitor BKI-1294

by Pablo Winzer, Nicoleta Anghel, Dennis Imhof, Vreni Balmer, Luis-Miguel Ortega-Mora, Kayode K. Ojo, Wesley C. Van Voorhis, Joachim Müller and Andrew Hemphill

Pathogens 2020, 9(5), 382; https://doi.org/10.3390/pathogens9050382 - 16 May 2020

Cited by 15 | Viewed by 2743

Abstract

Background: Bumped kinase inhibitors (BKIs) are potential drugs for neosporosis treatment in farm animals. BKI-1294 exposure results in the formation of multinucleated complexes (MNCs), which remain viable in vitro under constant drug pressure. We investigated the formation of BKI-1294 induced MNCs, the re-emergence [...] Read more.

Background: Bumped kinase inhibitors (BKIs) are potential drugs for neosporosis treatment in farm animals. BKI-1294 exposure results in the formation of multinucleated complexes (MNCs), which remain viable in vitro under constant drug pressure. We investigated the formation of BKI-1294 induced MNCs, the re-emergence of viable tachyzoites following drug removal, and the localization of CDPK1, the molecular target of BKIs. Methods: N. caninum tachyzoites and MNCs were studied by TEM and immunofluorescence using antibodies directed against CDPK1, and against NcSAG1 and IMC1 as markers for tachyzoites and newly formed zoites, respectively. Results: After six days of drug exposure, MNCs lacked SAG1 surface expression but remained intracellular, and formed numerous zoites incapable of disjoining from each other. Following drug removal, proliferation continued, and zoites lacking NcSAG1 emerged from the periphery of these complexes, forming infective tachyzoites after 10 days. In intracellular tachyzoites, CDPK1 was evenly distributed but shifted towards the apical part once parasites were extracellular. This shift was not affected by BKI-1294. Conclusions: CDPK1 has a dynamic distribution depending on whether parasites are located within a host cell or outside. During MNC-to-tachyzoite reconversion newly formed tachyzoites are generated directly from MNCs through zoites of unknown surface antigen composition. Further in vivo studies are needed to determine if MNCs could lead to a persistent reservoir of infection after BKI treatment. Full article

(This article belongs to the Special Issue Neospora Caninum: Infection and Immunity)

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16 pages, 1016 KiB

Open AccessEditor’s ChoiceArticle

Leptospira Survey in Wild Boar (Sus scrofa) Hunted in Tuscany, Central Italy

by Giovanni Cilia, Fabrizio Bertelloni, Marta Angelini, Domenico Cerri and Filippo Fratini

Pathogens 2020, 9(5), 377; https://doi.org/10.3390/pathogens9050377 - 14 May 2020

Cited by 22 | Viewed by 3322

Abstract

Leptospirosis is a re-emerging, worldwide zoonosis, and wild boar (Sus scrofa) are involved in its epidemiology as the reservoir. The aim of this study was to investigate the prevalence of Leptospira with serological, bacteriological, and molecular assays in wild boar hunted [...] Read more.

Leptospirosis is a re-emerging, worldwide zoonosis, and wild boar (Sus scrofa) are involved in its epidemiology as the reservoir. The aim of this study was to investigate the prevalence of Leptospira with serological, bacteriological, and molecular assays in wild boar hunted in Tuscany (Italy) during two hunting seasons. In total, 287 specimens of sera, kidneys, and liver were collected to perform microscopic agglutination tests (MATs), isolation, and RealTime PCR to detect pathogenic (lipL32 gene), intermediate (16S rRNA gene), and saprophytic (23S rRNA gene) Leptospira. Within sera, 39 (13.59%) were positive to the MAT, and Australis was the most represented serogroup (4.88%), followed by Pomona (4.18%), and Tarassovi (3.14%). Moreover, four Leptospira cultures were positive, and once isolates were identified, one was identified as L. borgpetersenii serovar Tarassovi, and three as L. interrogans serovar Bratislava. Pathogenic Leptospira DNA were detected in 32 wild boar kidneys (11.15%). The characterization through the amplification of the rrs2 gene highlighted their belonging to L. interrogans (23 kidneys), L. borgpetersenii (four), and L. kirschneri (one), while nine kidneys (3.14%) were positive for intermediate Leptospira, all belonging to L. fainei. The results of this study confirmed the importance of wild boar in the epidemiology of leptospirosis among wildlife in Central Italy. Full article

(This article belongs to the Special Issue Leptospira infections in Domestic and Wild Animal)

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17 pages, 7667 KiB

Open AccessEditor’s ChoiceArticle

Identification of Transmission Routes of Campylobacter and On-Farm Measures to Reduce Campylobacter in Chicken

by Sara Frosth, Oskar Karlsson-Lindsjö, Adnan Niazi, Lise-Lotte Fernström and Ingrid Hansson

Pathogens 2020, 9(5), 363; https://doi.org/10.3390/pathogens9050363 - 09 May 2020

Cited by 26 | Viewed by 4509

Abstract

An in-depth analysis was performed on Swedish broiler producers that had delivered chickens with Campylobacter to slaughter over several years, in order to identify possible transmission routes and formulate effective measures to prevent chickens being colonized with Campylobacter. Between 2017 and 2019, 626 [...] Read more.

An in-depth analysis was performed on Swedish broiler producers that had delivered chickens with Campylobacter to slaughter over several years, in order to identify possible transmission routes and formulate effective measures to prevent chickens being colonized with Campylobacter. Between 2017 and 2019, 626 samples were collected at farm level and Campylobacter was isolated from 133 (21.2%). All C. jejuni and C. coli isolated from these samples were whole-genome sequenced, together with isolates from the corresponding cecum samples at slaughter (n = 256). Core genome multi-locus sequence typing (cgMLST) analysis, using schemes consisting of 1140 and 529 genes for C. jejuni and C. coli, respectively, revealed that nearby cattle, contaminated drinking water, water ponds, transport crates, and parent flocks were potential reservoirs of Campylobacter. A novel feature compared with previous studies is that measures were implemented and tested during the work. These contributed to a nationwide decrease in Campylobacter-positive flocks from 15.4% in 2016 to 4.6% in 2019, which is the lowest ever rate in Sweden. To conclude, there are different sources and routes of Campylobacter transmission to chickens from different broiler producers, and individual measures must be taken by each producer to prevent Campylobacter colonization of chickens. Full article

(This article belongs to the Special Issue Campylobacter Infections)

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15 pages, 5349 KiB

Open AccessEditor’s ChoiceArticle

Silver Nanoparticles as a Novel Potential Preventive Agent against Acanthamoeba Keratitis

by Edyta B. Hendiger, Marcin Padzik, Ines Sifaoui, María Reyes-Batlle, Atteneri López-Arencibia, Aitor Rizo-Liendo, Carlos J. Bethencourt-Estrella, Desirée San Nicolás-Hernández, Olfa Chiboub, Rubén L. Rodríguez-Expósito, Marta Grodzik, Anna Pietruczuk-Padzik, Karolina Stępień, Gabriela Olędzka, Lidia Chomicz, José E. Piñero and Jacob Lorenzo-Morales

Pathogens 2020, 9(5), 350; https://doi.org/10.3390/pathogens9050350 - 05 May 2020

Cited by 23 | Viewed by 3571

Abstract

Free living, cosmopolitan amoebae from Acanthamoeba genus present a serious risk to human health. As facultative human parasites, these amoebae may cause Acanthamoeba keratitis (AK). Acanthamoeba keratitis is a severe, vision-threatening corneal infection with non-specific symptoms. The number of reported AK cases worldwide [...] Read more.

Free living, cosmopolitan amoebae from Acanthamoeba genus present a serious risk to human health. As facultative human parasites, these amoebae may cause Acanthamoeba keratitis (AK). Acanthamoeba keratitis is a severe, vision-threatening corneal infection with non-specific symptoms. The number of reported AK cases worldwide has been increasing every year. Moreover, 90% of Acanthamoeba keratitis cases are related to contact lens use. Wearing and storage contact lenses not in accordance with the physicians and manufacturers recommendations are the primary key risk factors of this disease. Amoebae can easily adhere to the contact lens surface and transmit to the corneal epithelium. Preventing amoebae adhesion to the contact lens surface could significantly decrease the number of AK infections. Until now, the effective therapy against AK is still under development. Currently proposed therapies are mainly limited to the chlorhexidine digluconate combined with propamidine isethionate or hexamidine applications, which are insufficient and very toxic to the eye. Due to lack of effective treatment, looking for new potential preventive agents is crucial to decrease the number of Acanthamoeba keratitis infections, especially among contact lens users. Nanoparticles have been already included in several novel therapies against bacteria, viruses, fungi, and protist. However, their anti-amoebic potential has not been fully tested yet. The aim of this study was to assess silver nanoparticles (AgNPs) and platinum nanoparticles (PtNPs) anti-amoebic activity and influence on the amoebae adhesion to the surface of four different groups of contact lenses—classified according to the Food and Drugs Administration (FDA) guidelines. The obtained results show that both tested nanoparticles were effective against Acanthamoeba trophozoites and decreased the amoebae adhesion to the contact lens surface. AgNPs showed better anti-amoebic activity to cytotoxicity dependence and reduced amoebae adhesion in a wider spectrum of the tested contact lenses. Our studies also confirmed that ionization next to hydration of the contact lens material is a crucial parameter influencing the Acanthamoeba adhesion to the contact lens surface. In conclusion, silver nanoparticles might be considered as a novel preventive agent against Acanthamoeba keratitis infection. Full article

(This article belongs to the Special Issue Selected Papers from the International Meeting on the Biology and Pathogenicity of Free-Living Amoebae (FLAM2019))

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13 pages, 1908 KiB

Open AccessEditor’s ChoiceArticle

Evaluation of Volatile Organic Compounds Obtained from Breath and Feces to Detect Mycobacterium tuberculosis Complex in Wild Boar (Sus scrofa) in Doñana National Park, Spain

by Pauline Nol, Radu Ionescu, Tesfalem Geremariam Welearegay, Jose Angel Barasona, Joaquin Vicente, Kelvin de Jesus Beleño-Sáenz, Irati Barrenetxea, Maria Jose Torres, Florina Ionescu and Jack Rhyan

Pathogens 2020, 9(5), 346; https://doi.org/10.3390/pathogens9050346 - 02 May 2020

Cited by 11 | Viewed by 2827

Abstract

The presence of Mycobacterium tuberculosis complex (MTBC) in wild swine, such as in wild boar (Sus scrofa) in Eurasia, is cause for serious concern. Development of accurate, efficient, and noninvasive methods to detect MTBC in wild swine would be highly beneficial [...] Read more.

The presence of Mycobacterium tuberculosis complex (MTBC) in wild swine, such as in wild boar (Sus scrofa) in Eurasia, is cause for serious concern. Development of accurate, efficient, and noninvasive methods to detect MTBC in wild swine would be highly beneficial to surveillance and disease management efforts in affected populations. Here, we describe the first report of identification of volatile organic compounds (VOC) obtained from the breath and feces of wild boar to distinguish between MTBC-positive and MTBC-negative boar. We analyzed breath and fecal VOC collected from 15 MTBC-positive and 18 MTBC-negative wild boar in Donaña National Park in Southeast Spain. Analyses were divided into three age classes, namely, adults (>2 years), sub-adults (12–24 months), and juveniles (<12 months). We identified significant compounds by applying the two-tailed statistical t-test for two samples assuming unequal variance, with an α value of 0.05. One statistically significant VOC was identified in breath samples from adult wild boar and 14 were identified in breath samples from juvenile wild boar. One statistically significant VOC was identified in fecal samples collected from sub-adult wild boar and three were identified in fecal samples from juvenile wild boar. In addition, discriminant function analysis (DFA) was used to build classification models for MTBC prediction in juvenile animals. Using DFA, we were able to distinguish between MTBC-positive juvenile wild boar and MTBC-negative juvenile wild boar using breath VOC or fecal VOC. Based on our results, further research is warranted and should be performed using larger sample sizes, as well as wild boar from various geographic locations, to verify these compounds as biomarkers for MTBC infection in this species. This new approach to detect MTBC infection in free-ranging wild boar potentially comprises a reliable and efficient screening tool for surveillance in animal populations. Full article

(This article belongs to the Special Issue Tuberculosis Epidemiology and Control in Multi-Host Systems)

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21 pages, 3014 KiB

Open AccessEditor’s ChoiceReview

Pathogenomics and Management of Fusarium Diseases in Plants

by Sephra N. Rampersad

Pathogens 2020, 9(5), 340; https://doi.org/10.3390/pathogens9050340 - 01 May 2020

Cited by 61 | Viewed by 6742

Abstract

There is an urgency to supplant the heavy reliance on chemical control of Fusarium diseases in different economically important, staple food crops due to development of resistance in the pathogen population, the high cost of production to the risk-averse grower, and the concomitant [...] Read more.

There is an urgency to supplant the heavy reliance on chemical control of Fusarium diseases in different economically important, staple food crops due to development of resistance in the pathogen population, the high cost of production to the risk-averse grower, and the concomitant environmental impacts. Pathogenomics has enabled (i) the creation of genetic inventories which identify those putative genes, regulators, and effectors that are associated with virulence, pathogenicity, and primary and secondary metabolism; (ii) comparison of such genes among related pathogens; (iii) identification of potential genetic targets for chemical control; and (iv) better characterization of the complex dynamics of host–microbe interactions that lead to disease. This type of genomic data serves to inform host-induced gene silencing (HIGS) technology for targeted disruption of transcription of select genes for the control of Fusarium diseases. This review discusses the various repositories and browser access points for comparison of genomic data, the strategies for identification and selection of pathogenicity- and virulence-associated genes and effectors in different Fusarium species, HIGS and successful Fusarium disease control trials with a consideration of loss of RNAi, off-target effects, and future challenges in applying HIGS for management of Fusarium diseases. Full article

(This article belongs to the Special Issue Fusarium: Pathogenomics and Inherent Resistance)

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14 pages, 715 KiB

Open AccessEditor’s ChoiceReview

Antiretroviral Therapy in HTLV-1 Infection: An Updated Overview

by Francesca Marino-Merlo, Emanuela Balestrieri, Claudia Matteucci, Antonio Mastino, Sandro Grelli and Beatrice Macchi

Pathogens 2020, 9(5), 342; https://doi.org/10.3390/pathogens9050342 - 01 May 2020

Cited by 25 | Viewed by 4113

Abstract

The human T cell leukemic/lymphotropic virus type 1 (HTLV-1), discovered several years ago, is the causative agent for a rapid progressive haematological malignancy, adult T cell leukemia (ATL), for debilitating neurological diseases and for a number of inflammatory based diseases. Although the heterogeneous [...] Read more.

The human T cell leukemic/lymphotropic virus type 1 (HTLV-1), discovered several years ago, is the causative agent for a rapid progressive haematological malignancy, adult T cell leukemia (ATL), for debilitating neurological diseases and for a number of inflammatory based diseases. Although the heterogeneous features of the diseases caused by HTLV-1, a common topic concerning related therapeutic treatments relies on the use of antiretrovirals. This review will compare the different approaches and opinions in this matter, giving a concise overview of preclinical as well as clinical studies covering all the aspects of antiretrovirals in HTLV-1 infection. Studies will be grouped on the basis of the class of antiretroviral, putting together both pre-clinical and clinical results and generally following a chronological order. Analysis of the existing literature highlights that a number of preclinical studies clearly demonstrate that different classes of antiretrovirals, already utilized as anti-HIV agents, are actually capable to efficiently contrast HTLV-1 infection. Nevertheless, the results of most of the clinical studies are generally discouraging on the same point. In conclusion, the design of new antiretrovirals more specifically focused on HTLV-1 targets, and/or the establishment of early treatments with antiretrovirals could hopefully change the perspectives of diseases caused by HTLV-1. Full article

(This article belongs to the Special Issue HTLV-1 Disease)

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16 pages, 4062 KiB

Open AccessEditor’s ChoiceArticle

Genetic Diversity and Sequence Polymorphism of Two Genes Encoding Theileria parva Antigens Recognized by CD8⁺ T Cells among Vaccinated and Unvaccinated Cattle in Malawi

by Elisha Chatanga, Kyoko Hayashida, Walter Muleya, Kodai Kusakisako, Mohamed Abdallah Mohamed Moustafa, Bashir Salim, Ken Katakura, Chihiro Sugimoto, Nariaki Nonaka and Ryo Nakao

Pathogens 2020, 9(5), 334; https://doi.org/10.3390/pathogens9050334 - 30 Apr 2020

Cited by 10 | Viewed by 3243

Abstract

East Coast fever (ECF) is an acute fatal tick-borne disease of cattle caused by Theileria parva. It causes major losses in exotic and crossbreed cattle, but this could be prevented by a vaccine of T. parva if the vaccine is selected properly [...] Read more.

East Coast fever (ECF) is an acute fatal tick-borne disease of cattle caused by Theileria parva. It causes major losses in exotic and crossbreed cattle, but this could be prevented by a vaccine of T. parva if the vaccine is selected properly based on information from molecular epidemiology studies. The Muguga cocktail (MC) vaccine (Muguga, Kiambu 5 and Serengeti-transformed strains) has been used on exotic and crossbreed cattle. A total of 254 T. parva samples from vaccinated and unvaccinated cattle were used to understand the genetic diversity of T. parva in Malawi using partial sequences of the Tp1 and Tp2 genes encoding T. parva CD8⁺ antigens, known to be immunodominant and current candidate antigens for a subunit vaccine. Single nucleotide polymorphisms were observed at 14 positions (3.65%) in Tp1 and 156 positions (33.12%) in Tp2, plus short deletions in Tp1, resulting in 6 and 10 amino acid variants in the Tp1 and Tp2 genes, respectively. Most sequences were either identical or similar to T. parva Muguga and Kiambu 5 strains. This may suggest the possible expansion of vaccine components into unvaccinated cattle, or that a very similar genotype already existed in Malawi. This study provides information that support the use of MC to control ECF in Malawi. Full article

(This article belongs to the Section Animal Pathogens)

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17 pages, 1377 KiB

Open AccessEditor’s ChoiceArticle

Vaccine-Mediated Mechanisms Controlling Francisella tularensis SCHU S4 Growth in a Rat Co-Culture System

by Helena Lindgren, Kjell Eneslätt, Igor Golovliov, Carl Gelhaus, Patrik Rydén, Terry Wu and Anders Sjöstedt

Pathogens 2020, 9(5), 338; https://doi.org/10.3390/pathogens9050338 - 30 Apr 2020

Cited by 7 | Viewed by 2068

Abstract

Francisella tularensis causes the severe disease tularemia. In the present study, the aim was to identify correlates of protection in the rat co-culture model by investigating the immune responses using two vaccine candidates conferring distinct degrees of protection in rat and mouse models. [...] Read more.

Francisella tularensis causes the severe disease tularemia. In the present study, the aim was to identify correlates of protection in the rat co-culture model by investigating the immune responses using two vaccine candidates conferring distinct degrees of protection in rat and mouse models. The immune responses were characterized by use of splenocytes from naïve or Live vaccine strain- (LVS) or ∆clpB/∆wbtC-immunized Fischer 344 rats as effectors and bone marrow-derived macrophages infected with the highly virulent strain SCHU S4. A complex immune response was elicited, resulting in cytokine secretion, nitric oxide production, and efficient control of the intracellular bacterial growth. Addition of LVS-immune splenocytes elicited a significantly better control of bacterial growth than ∆clpB/∆wbtC splenocytes. This mirrored the efficacy of the vaccine candidates in the rat model. Lower levels of IFN-γ, TNF, fractalkine, IL-2, and nitrite were present in the co-cultures with ∆clpB/∆wbtC splenocytes than in those with splenocytes from LVS-immunized rats. Nitric oxide was found to be a correlate of protection, since the levels inversely correlated to the degree of protection and inhibition of nitric oxide production completely reversed the growth inhibition of SCHU S4. Overall, the results demonstrate that the co-culture assay with rat-derived cells is a suitable model to identify correlates of protection against highly virulent strains of F. tularensis Full article

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13 pages, 2502 KiB

Open AccessEditor’s ChoiceArticle

The Role of the Maridi Dam in Causing an Onchocerciasis-Associated Epilepsy Epidemic in Maridi, South Sudan: An Epidemiological, Sociological, and Entomological Study

by T. L. Lakwo, S. Raimon, M. Tionga, J. N. Siewe Fodjo, P. Alinda, W. J. Sebit, J. Y. Carter and R. Colebunders

Pathogens 2020, 9(4), 315; https://doi.org/10.3390/pathogens9040315 - 24 Apr 2020

Cited by 30 | Viewed by 4622

Abstract

Background: An epilepsy prevalence of 4.4% was documented in onchocerciasis-endemic villages close to the Maridi River in South Sudan. We investigated the role of the Maridi dam in causing an onchocerciasis-associated epilepsy epidemic in these villages. Methods: Affected communities were visited [...] Read more.

Background: An epilepsy prevalence of 4.4% was documented in onchocerciasis-endemic villages close to the Maridi River in South Sudan. We investigated the role of the Maridi dam in causing an onchocerciasis-associated epilepsy epidemic in these villages. Methods: Affected communities were visited in November 2019 to conduct focus group discussions with village elders and assess the OV16 seroprevalence in 3- to 9-year-old children. Entomological assessments to map blackfly breeding sites and determine biting rates around the Maridi River were conducted. Historical data regarding various activities at the Maridi dam were obtained from the administrative authorities. Results: The Maridi dam was constructed in 1954–1955. Village elders reported an increasing number of children developing epilepsy, including nodding syndrome, from the early 1990s. Kazana 2 (the village closest to the dam; epilepsy prevalence 11.9%) had the highest OV16 seroprevalence: 40.0% among children 3–6 years old and 66.7% among children 7–9 years old. The Maridi dam spillway was found to be the only Simulium damnosum breeding site along the river, with biting rates reaching 202 flies/man/h. Conclusion: Onchocerciasis transmission rates are high in Maridi. Suitable breeding conditions at the Maridi dam, coupled with suboptimal onchocerciasis control measures, have probably played a major role in causing an epilepsy (including nodding syndrome) epidemic in the Maridi area. Full article

(This article belongs to the Special Issue Onchocerciasis and River Epilepsy)

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17 pages, 3831 KiB

Open AccessEditor’s ChoiceArticle

Venereal Transmission of Vesicular Stomatitis Virus by Culicoides sonorensis Midges

by Paula Rozo-Lopez, Berlin Londono-Renteria and Barbara S. Drolet

Pathogens 2020, 9(4), 316; https://doi.org/10.3390/pathogens9040316 - 24 Apr 2020

Cited by 16 | Viewed by 6461

Abstract

Culicoides sonorensis biting midges are well-known agricultural pests and transmission vectors of arboviruses such as vesicular stomatitis virus (VSV). The epidemiology of VSV is complex and encompasses a broad range of vertebrate hosts, multiple routes of transmission, and diverse vector species. In temperate [...] Read more.

Culicoides sonorensis biting midges are well-known agricultural pests and transmission vectors of arboviruses such as vesicular stomatitis virus (VSV). The epidemiology of VSV is complex and encompasses a broad range of vertebrate hosts, multiple routes of transmission, and diverse vector species. In temperate regions, viruses can overwinter in the absence of infected animals through unknown mechanisms, to reoccur the next year. Non-conventional routes for VSV vector transmission may help explain viral maintenance in midge populations during inter-epidemic periods and times of adverse conditions for bite transmission. In this study, we examined whether VSV could be transmitted venereally between male and female midges. Our results showed that VSV-infected females could venereally transmit virus to uninfected naïve males at a rate as high as 76.3% (RT-qPCR), 31.6% (virus isolation) during the third gonotrophic cycle. Additionally, VSV-infected males could venereally transmit virus to uninfected naïve females at a rate as high as 76.6% (RT-qPCR), 49.2% (virus isolation). Immunofluorescent staining of micro-dissected reproductive organs, immunochemical staining of midge histological sections, examination of internal reproductive organ morphology, and observations of mating behaviors were used to determine relevant anatomical sites for virus location and to hypothesize the potential mechanism for VSV transmission in C. sonorensis midges through copulation. Full article

(This article belongs to the Special Issue Untargeted Alternative Routes of Arbovirus Transmission)

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9 pages, 1207 KiB

Open AccessEditor’s ChoiceArticle

Long-Term Incubation PrP^CWD with Soils Affects Prion Recovery but Not Infectivity

by Alsu Kuznetsova, Debbie McKenzie, Catherine Cullingham and Judd M. Aiken

Pathogens 2020, 9(4), 311; https://doi.org/10.3390/pathogens9040311 - 23 Apr 2020

Cited by 15 | Viewed by 3815

Abstract

Chronic wasting disease (CWD) is a contagious prion disease of cervids. The infectious agent is shed from animals at the preclinical and clinical stages of disease where it persists in the environment as a reservoir of CWD infectivity. In this study, we demonstrate [...] Read more.

Chronic wasting disease (CWD) is a contagious prion disease of cervids. The infectious agent is shed from animals at the preclinical and clinical stages of disease where it persists in the environment as a reservoir of CWD infectivity. In this study, we demonstrate that long-term incubation of CWD prions (generated from tg-mice infected with deer or elk prions) with illite, montmorillonite (Mte) and whole soils results in decreased recovery of PrP^CWD, suggesting that binding becomes more avid and irreversible with time. This continual decline of immunoblot PrP^CWD detection did not correlate with prion infectivity levels. Bioassay showed no significant differences in incubation periods between mice inoculated with 1% CWD brain homogenate (BH) and with the CWD-BH pre-incubated with quartz or Luvisolic Ae horizon for 1 or 30 weeks. After 55 weeks incubation with Chernozem and Luvisol, bound PrP^CWD was not detectable by immunoblotting but remained infectious. This study shows that although recovery of PrP^CWD bound to soil minerals and whole soils with time become more difficult, prion infectivity is not significantly altered. Detection of prions in soil is, therefore, not only affected by soil type but also by length of time of the prion–soil interaction. Full article

(This article belongs to the Special Issue Prions and Prion-Like Transmissible Protein Pathogens)

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25 pages, 2278 KiB

Open AccessEditor’s ChoiceReview

Phenylpropanoid Pathway Engineering: An Emerging Approach towards Plant Defense

by Vivek Yadav, Zhongyuan Wang, Chunhua Wei, Aduragbemi Amo, Bilal Ahmed, Xiaozhen Yang and Xian Zhang

Pathogens 2020, 9(4), 312; https://doi.org/10.3390/pathogens9040312 - 23 Apr 2020

Cited by 209 | Viewed by 14242

Abstract

Pathogens hitting the plant cell wall is the first impetus that triggers the phenylpropanoid pathway for plant defense. The phenylpropanoid pathway bifurcates into the production of an enormous array of compounds based on the few intermediates of the shikimate pathway in response to [...] Read more.

Pathogens hitting the plant cell wall is the first impetus that triggers the phenylpropanoid pathway for plant defense. The phenylpropanoid pathway bifurcates into the production of an enormous array of compounds based on the few intermediates of the shikimate pathway in response to cell wall breaches by pathogens. The whole metabolomic pathway is a complex network regulated by multiple gene families and it exhibits refined regulatory mechanisms at the transcriptional, post-transcriptional, and post-translational levels. The pathway genes are involved in the production of anti-microbial compounds as well as signaling molecules. The engineering in the metabolic pathway has led to a new plant defense system of which various mechanisms have been proposed including salicylic acid and antimicrobial mediated compounds. In recent years, some key players like phenylalanine ammonia lyases (PALs) from the phenylpropanoid pathway are proposed to have broad spectrum disease resistance (BSR) without yield penalties. Now we have more evidence than ever, yet little understanding about the pathway-based genes that orchestrate rapid, coordinated induction of phenylpropanoid defenses in response to microbial attack. It is not astonishing that mutants of pathway regulator genes can show conflicting results. Therefore, precise engineering of the pathway is an interesting strategy to aim at profitably tailored plants. Here, this review portrays the current progress and challenges for phenylpropanoid pathway-based resistance from the current prospective to provide a deeper understanding. Full article

(This article belongs to the Special Issue Genomics, Molecular, Genetics, and Diversity of Plant Disease Resistance)

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26 pages, 4754 KiB

Open AccessEditor’s ChoiceReview

Mosquito-Borne Diseases Emergence/Resurgence and How to Effectively Control It Biologically

by Handi Dahmana and Oleg Mediannikov

Pathogens 2020, 9(4), 310; https://doi.org/10.3390/pathogens9040310 - 23 Apr 2020

Cited by 80 | Viewed by 15284

Abstract

Deadly pathogens and parasites are transmitted by vectors and the mosquito is considered the most threatening vector in public health, transmitting these pathogens to humans and animals. We are currently witnessing the emergence/resurgence in new regions/populations of the most important mosquito-borne diseases, such [...] Read more.

Deadly pathogens and parasites are transmitted by vectors and the mosquito is considered the most threatening vector in public health, transmitting these pathogens to humans and animals. We are currently witnessing the emergence/resurgence in new regions/populations of the most important mosquito-borne diseases, such as arboviruses and malaria. This resurgence may be the consequence of numerous complex parameters, but the major cause remains the mismanagement of insecticide use and the emergence of resistance. Biological control programmes have rendered promising results but several highly effective techniques, such as genetic manipulation, remain insufficiently considered as a control mechanism. Currently, new strategies based on attractive toxic sugar baits and new agents, such as Wolbachia and Asaia, are being intensively studied for potential use as alternatives to chemicals. Research into new insecticides, Insect Growth Regulators, and repellent compounds is pressing, and the improvement of biological strategies may provide key solutions to prevent outbreaks, decrease the danger to at-risk populations, and mitigate resistance. Full article

(This article belongs to the Special Issue Translational Research for Zoonotic Parasites: New Findings toward Improved Diagnostics, Therapy and Prevention)

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13 pages, 866 KiB

Open AccessEditor’s ChoiceReview

Origin, Potential Therapeutic Targets and Treatment for Coronavirus Disease (COVID-19)

by Muhammad Shahid Nadeem, Mazin A. Zamzami, Hani Choudhry, Bibi Nazia Murtaza, Imran Kazmi, Habib Ahmad and Abdul Rauf Shakoori

Pathogens 2020, 9(4), 307; https://doi.org/10.3390/pathogens9040307 - 22 Apr 2020

Cited by 62 | Viewed by 16831

Abstract

The ongoing episode of coronavirus disease 19 (COVID-19) has imposed a serious threat to global health and the world economy. The disease has rapidly acquired a pandemic status affecting almost all populated areas of the planet. The causative agent of COVID-19 is a [...] Read more.

The ongoing episode of coronavirus disease 19 (COVID-19) has imposed a serious threat to global health and the world economy. The disease has rapidly acquired a pandemic status affecting almost all populated areas of the planet. The causative agent of COVID-19 is a novel coronavirus known as SARS-CoV-2. The virus has an approximate 30 kb single-stranded positive-sense RNA genome, which is 74.5% to 99% identical to that of SARS-CoV, CoV-pangolin, and the coronavirus the from horseshoe bat. According to available information, SARS-CoV-2 is inferred to be a recombinant virus that originated from bats and was transmitted to humans, possibly using the pangolin as the intermediate host. The interaction of the SARS-CoV-2 spike protein with the human ACE2 (angiotensin-converting enzyme 2) receptor, and its subsequent cleavage by serine protease and fusion, are the main events in the pathophysiology. The serine protease inhibitors, spike protein-based vaccines, or ACE2 blockers may have therapeutic potential in the near future. At present, no vaccine is available against COVID-19. The disease is being treated with antiviral, antimalarial, anti-inflammatory, herbal medicines, and active plasma antibodies. In this context, the present review article provides a cumulative account of the recent information regarding the viral characteristics, potential therapeutic targets, treatment options, and prospective research questions. Full article

(This article belongs to the Section Human Pathogens)

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14 pages, 905 KiB

Open AccessEditor’s ChoiceReview

Effects of Mycoplasmas on the Host Cell Signaling Pathways

by Sergei N. Borchsenius, Innokentii E. Vishnyakov, Olga A. Chernova, Vladislav M. Chernov and Nikolai A. Barlev

Pathogens 2020, 9(4), 308; https://doi.org/10.3390/pathogens9040308 - 22 Apr 2020

Cited by 15 | Viewed by 5140

Abstract

Mycoplasmas are the smallest free-living organisms. Reduced sizes of their genomes put constraints on the ability of these bacteria to live autonomously and make them highly dependent on the nutrients produced by host cells. Importantly, at the organism level, mycoplasmal infections may cause [...] Read more.

Mycoplasmas are the smallest free-living organisms. Reduced sizes of their genomes put constraints on the ability of these bacteria to live autonomously and make them highly dependent on the nutrients produced by host cells. Importantly, at the organism level, mycoplasmal infections may cause pathological changes to the host, including cancer and severe immunological reactions. At the molecular level, mycoplasmas often activate the NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) inflammatory response and concomitantly inhibit the p53-mediated response, which normally triggers the cell cycle and apoptosis. Thus, mycoplasmal infections may be considered as cancer-associated factors. At the same time, mycoplasmas through their membrane lipoproteins (LAMPs) along with lipoprotein derivatives (lipopeptide MALP-2, macrophage-activating lipopeptide-2) are able to modulate anti-inflammatory responses via nuclear translocation and activation of Nrf2 (the nuclear factor-E2-related anti-inflammatory transcription factor 2). Thus, interactions between mycoplasmas and host cells are multifaceted and depend on the cellular context. In this review, we summarize the current information on the role of mycoplasmas in affecting the host’s intracellular signaling mediated by the interactions between transcriptional factors p53, Nrf2, and NF-κB. A better understanding of the mechanisms underlying pathologic processes associated with reprogramming eukaryotic cells that arise during the mycoplasma-host cell interaction should facilitate the development of new therapeutic approaches to treat oncogenic and inflammatory processes. Full article

(This article belongs to the Collection Biomarkers and Pathogenesis of Infectious and Autoimmune Diseases)

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12 pages, 409 KiB

Open AccessEditor’s ChoiceArticle

Prevention and Control of Legionella and Pseudomonas spp. Colonization in Dental Units

by Benedetta Tuvo, Michele Totaro, Maria Luisa Cristina, Anna Maria Spagnolo, David Di Cave, Sara Profeti, Angelo Baggiani, Gaetano Privitera and Beatrice Casini

Pathogens 2020, 9(4), 305; https://doi.org/10.3390/pathogens9040305 - 21 Apr 2020

Cited by 24 | Viewed by 3418

Abstract

Introduction: Dental Unit Waterlines (DUWLs) have shown to be a source of Legionella infection. We report the experience of different dental healthcare settings where a risk management plan was implemented. Materials and methods: In a Hospital Odontostomatology Clinic (HOC) and three Private Dental [...] Read more.

Introduction: Dental Unit Waterlines (DUWLs) have shown to be a source of Legionella infection. We report the experience of different dental healthcare settings where a risk management plan was implemented. Materials and methods: In a Hospital Odontostomatology Clinic (HOC) and three Private Dental Clinics (PDCs) housing 13 and six dental units (DUs), respectively, an assessment checklist was applied to evaluate staff compliance with guideline recommendations. DUWLs microbial parameters were investigated before and after the application of corrective actions. Results: In the HOC a poor adherence to good practices was demonstrated, whereas protocols were carefully applied in PDCs. L. pneumophila sg 2–15 was isolated in 31% (4/13) and 33% (2/6) of DUs in HOC and PDCs, respectively, mainly from handpieces (32%, 6/19) with counts >10² colony-forming units per milliliter (CFU/L), often associated with P. aeruginosa (68%, 13/19). The shock disinfection with 3% v/v hydrogen peroxide (HP) showed a limited effect, with a recolonization period of about 4 weeks. Legionella was eradicated only after 6% v/v HP shock disinfection and filters-installation, whilst P. aeruginosa after the third shock disinfection with a solution of 4% v/v HP and biodegradable surfactants. Conclusions: Our data demonstrate the presence and persistence of microbial contamination within the DUWLs, which required strict adherence to control measures and the choice of effective disinfectants. Full article

(This article belongs to the Special Issue Legionella Contamination in Water Environment)

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16 pages, 2093 KiB

Open AccessEditor’s ChoiceArticle

Molecular Characterization and Antimicrobial Susceptibility of C. jejuni Isolates from Italian Wild Bird Populations

by Francesca Marotta, Anna Janowicz, Lisa Di Marcantonio, Claudia Ercole, Guido Di Donato, Giuliano Garofolo and Elisabetta Di Giannatale

Pathogens 2020, 9(4), 304; https://doi.org/10.3390/pathogens9040304 - 20 Apr 2020

Cited by 13 | Viewed by 3006

Abstract

Poultry is considered a major reservoir of human campylobacteriosis. It also been reported that not only poultry, but also wild birds, are capable of carrying C. jejuni, thus demonstrating to be a risk of spreading the bacteria in the environment. To gain [...] Read more.

Poultry is considered a major reservoir of human campylobacteriosis. It also been reported that not only poultry, but also wild birds, are capable of carrying C. jejuni, thus demonstrating to be a risk of spreading the bacteria in the environment. To gain insight into the population structure and investigate the antimicrobial resistance genotypes and phenotypes, we analyzed a collection of 135 C. jejuni from 15 species of wild birds in Italy. MLST revealed the presence of 41 sequence types (STs) and 13 clonal complexes (CCs). ST-179 complex and the generalist ST-45 complex were the most prevalent. Core genome MLST revealed that C. jejuni from ST-45 complex clustered according to the bird species, unlike the ST-179 complex which featured 3 different species in the same cluster. Overall we found a moderate prevalence of resistance to tetracycline (12.5%), ciprofloxacin and nalidixic acid (10%). The novel ST isolated from one pigeon showed resistance to all the antibiotics tested. The ST-179 complex (33.3%) was identified with significantly higher nalidixic acid resistance relative to other tested STs. Nine AMR genes (tet(O), cmeA, cmeB, cmeC, cmeR, aad, blaOXA-61, blaOXA-184 and erm(B)) and 23S rRNA and gyrA-associated point mutations were also described, indicating a concordance level between genotypic and phenotypic resistance of 23.3%, 23.4% and of 37.5% for streptomycin, tetracycline and quinolones/fluoroquinolones, respectively. We recommend that particular attention should be given to wild birds as key sentinel animals for the ecosystem contamination surveillance. Full article

(This article belongs to the Special Issue Campylobacter Infections)

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13 pages, 1620 KiB

Open AccessEditor’s ChoiceArticle

Evidence of the Extrahepatic Replication of Hepatitis E Virus in Human Endometrial Stromal Cells

by Mohamed A. El-Mokhtar, Essam R. Othman, Maha Y. Khashbah, Ali Ismael, Mohamed AA Ghaliony, Mohamed Ismail Seddik and Ibrahim M. Sayed

Pathogens 2020, 9(4), 295; https://doi.org/10.3390/pathogens9040295 - 17 Apr 2020

Cited by 26 | Viewed by 2869

Abstract

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide. The tropism of HEV is not restricted to the liver, and the virus replicates in other organs. Not all the extrahepatic targets for HEV are identified. Herein, we found [...] Read more.

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide. The tropism of HEV is not restricted to the liver, and the virus replicates in other organs. Not all the extrahepatic targets for HEV are identified. Herein, we found that non-decidualized primary human endometrial stromal cells (PHESCs), which are precursors for the decidua and placenta, are susceptible to HEV infection. PHESCs, isolated from healthy non-pregnant women (n = 5), were challenged with stool-derived HEV-1 and HEV-3. HEV RNA was measured by qPCR, and HEV capsid protein was assessed by flow cytometry, immunofluorescence (IF), and ELISA. HEV infection was successfully established in PHESCs. Intracellular and extracellular HEV RNA loads were increased over time, indicating efficient replication in vitro. In addition, HEV capsid protein was detected intracellularly in the HEV-infected PHESCs and accumulated extracellularly over time, confirming the viral assembly and release from the infected cells. HEV-1 replicated more efficiently in PHESCs than HEV-3 and induced more inflammatory responses. Ribavirin (RBV) treatment abolished the replication of HEV in PHESCs. In conclusion, PHESCs are permissive to HEV infection and these cells could be an endogenous source of HEV infection during pregnancy and mediate HEV vertical transmission. Full article

(This article belongs to the Special Issue Global Elimination of Viral Hepatitis)

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11 pages, 1018 KiB

Open AccessEditor’s ChoiceReview

Novel Coronavirus: Current Understanding of Clinical Features, Diagnosis, Pathogenesis, and Treatment Options

by Mohammad Ridwane Mungroo, Naveed Ahmed Khan and Ruqaiyyah Siddiqui

Pathogens 2020, 9(4), 297; https://doi.org/10.3390/pathogens9040297 - 17 Apr 2020

Cited by 37 | Viewed by 8815

Abstract

Since December 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in devastating consequences worldwide and infected more than 350,000 individuals and killed more than 16,000 people. SARS-CoV-2 is the seventh member of the coronavirus family [...] Read more.

Since December 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in devastating consequences worldwide and infected more than 350,000 individuals and killed more than 16,000 people. SARS-CoV-2 is the seventh member of the coronavirus family to affect humans. Symptoms of COVID-19 include fever (88%), cough (68%), vomiting (5%) and diarrhoea (3.7%), and transmission of SARS-CoV-2 is thought to occur from human to human via respiratory secretions released by the infected individuals when coughing and sneezing. COVID-19 can be detected through computed tomography scans and confirmed through molecular diagnostics tools such as polymerase chain reaction. Currently, there are no effective treatments against SARS-CoV-2, hence antiviral drugs have been used to reduce the development of respiratory complications by reducing viral load. The purpose of this review is to provide a comprehensive update on the pathogenesis, clinical aspects, diagnosis, challenges and treatment of SARS-CoV-2 infections. Full article

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20 pages, 1295 KiB

Open AccessEditor’s ChoiceReview

Subversion of Host Innate Immunity by Human Papillomavirus Oncoproteins

by Irene Lo Cigno, Federica Calati, Silvia Albertini and Marisa Gariglio

Pathogens 2020, 9(4), 292; https://doi.org/10.3390/pathogens9040292 - 17 Apr 2020

Cited by 38 | Viewed by 6406

Abstract

The growth of human papillomavirus (HPV)-transformed cells depends on the ability of the viral oncoproteins E6 and E7, especially those from high-risk HPV16/18, to manipulate the signaling pathways involved in cell proliferation, cell death, and innate immunity. Emerging evidence indicates that E6/E7 inhibition [...] Read more.

The growth of human papillomavirus (HPV)-transformed cells depends on the ability of the viral oncoproteins E6 and E7, especially those from high-risk HPV16/18, to manipulate the signaling pathways involved in cell proliferation, cell death, and innate immunity. Emerging evidence indicates that E6/E7 inhibition reactivates the host innate immune response, reversing what until then was an unresponsive cellular state suitable for viral persistence and tumorigenesis. Given that the disruption of distinct mechanisms of immune evasion is an attractive strategy for cancer therapy, the race is on to gain a better understanding of E6/E7-induced immune escape and cancer progression. Here, we review recent literature on the interplay between E6/E7 and the innate immune signaling pathways cGAS/STING/TBK1, RIG-I/MAVS/TBK1, and Toll-like receptors (TLRs). The overall emerging picture is that E6 and E7 have evolved broad-spectrum mechanisms allowing for the simultaneous depletion of multiple rather than single innate immunity effectors. The cGAS/STING/TBK1 pathway appears to be the most heavily impacted, whereas the RIG-I/MAVS/TBK1, still partially functional in HPV-transformed cells, can be activated by the powerful RIG-I agonist M8, triggering the massive production of type I and III interferons (IFNs), which potentiates chemotherapy-mediated cell killing. Overall, the identification of novel therapeutic targets to restore the innate immune response in HPV-transformed cells could transform the way HPV-associated cancers are treated. Full article

(This article belongs to the Special Issue Viral-host interactions and determinants of human papillomavirus (HPV) life cycle and pathogenesis)

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12 pages, 248 KiB

Open AccessEditor’s ChoiceReview

Updated Management Guidelines for Clostridioides difficile in Paediatrics

by Margherita Gnocchi, Martina Gagliardi, Pierpacifico Gismondi, Federica Gaiani, Gian Luigi de’ Angelis and Susanna Esposito

Pathogens 2020, 9(4), 291; https://doi.org/10.3390/pathogens9040291 - 16 Apr 2020

Cited by 17 | Viewed by 3876

Abstract

Clostridioides difficile, formerly known as Clostridium difficile, causes infections (CDI) varying from self-limited diarrhoea to severe conditions, including toxic megacolon and bowel perforation. For this reason, a prompt diagnosis is fundamental to early treatment and the prevention of transmission. The aim of [...] Read more.

Clostridioides difficile, formerly known as Clostridium difficile, causes infections (CDI) varying from self-limited diarrhoea to severe conditions, including toxic megacolon and bowel perforation. For this reason, a prompt diagnosis is fundamental to early treatment and the prevention of transmission. The aim of this article is to review diagnostic laboratory methods that are now available to detect C. difficile and to discuss the most recent recommendations on CDI treatment in children. Currently, there is no consensus on the best method for detecting C. difficile. Indeed, none of the available diagnostics possess at the same time high sensitivity and specificity, low cost and rapid turnaround times. Appropriate therapy is targeted according to age, severity and recurrence of the episode of infection, and the recent availability of new antibiotics opens new opportunities. De-escalation of antibiotics that are directly associated with CDI remains a priority and the cautious use of probiotics is recommended. Vancomycin represents the first-line therapy for CDI, although in children metronidazole can still be used as a first-line drug. Fidaxomicin is a new treatment option with equivalent initial response rates as vancomycin but lower relapse rates of CDI. Faecal microbiota transplantation should be considered for patients with multiple recurrences of CDI. Monoclonal antibodies and vaccines seem to represent a future perspective against CDI. However, only further studies will permit us to understand whether these new approaches could be effective in therapy and prevention of CDI in paediatric populations. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Clostridioides difficile)

15 pages, 932 KiB

Open AccessEditor’s ChoiceReview

The Role of Apoptin in Chicken Anemia Virus Replication

by Cynthia Feng, Yingke Liang and Jose G. Teodoro

Pathogens 2020, 9(4), 294; https://doi.org/10.3390/pathogens9040294 - 16 Apr 2020

Cited by 10 | Viewed by 4072

Abstract

Apoptin is the Vp3 protein of chicken anemia virus (CAV), which infects the thymocytes and erythroblasts in young chickens, causing chicken infectious anemia and immunosuppression. Apoptin is highly studied for its ability to selectively induce apoptosis in human tumor cells and, thus, is [...] Read more.

Apoptin is the Vp3 protein of chicken anemia virus (CAV), which infects the thymocytes and erythroblasts in young chickens, causing chicken infectious anemia and immunosuppression. Apoptin is highly studied for its ability to selectively induce apoptosis in human tumor cells and, thus, is a protein of interest in anti-tumor therapy. CAV apoptin is known to localize to different subcellular compartments in transformed and non-transformed cells, depending on the DNA damage response, and the phosphorylation of several identified threonine residues. In addition, apoptin interacts with molecular machinery such as the anaphase promoting complex/cyclosome (APC/C) to inhibit the cell cycle and induce arrest in G2/M phase. While these functions of apoptin contribute to the tumor-selective effect of the protein, they also provide an important fundamental framework to apoptin’s role in viral infection, pathogenesis, and propagation. Here, we reviewed how the regulation, localization, and functions of apoptin contribute to the viral life cycle and postulated its importance in efficient replication of CAV. A model of the molecular biology of infection is critical to informing our understanding of CAV and other related animal viruses that threaten the agricultural industry. Full article

(This article belongs to the Special Issue Chicken Anaemia Virus Infection)

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23 pages, 487 KiB

Open AccessEditor’s ChoiceReview

Legionella pneumophila and Protozoan Hosts: Implications for the Control of Hospital and Potable Water Systems

by Muhammad Atif Nisar, Kirstin E. Ross, Melissa H. Brown, Richard Bentham and Harriet Whiley

Pathogens 2020, 9(4), 286; https://doi.org/10.3390/pathogens9040286 - 15 Apr 2020

Cited by 28 | Viewed by 4065

Abstract

Legionella pneumophila is an opportunistic waterborne pathogen of public health concern. It is the causative agent of Legionnaires’ disease (LD) and Pontiac fever and is ubiquitous in manufactured water systems, where protozoan hosts and complex microbial communities provide protection from disinfection procedures. This [...] Read more.

Legionella pneumophila is an opportunistic waterborne pathogen of public health concern. It is the causative agent of Legionnaires’ disease (LD) and Pontiac fever and is ubiquitous in manufactured water systems, where protozoan hosts and complex microbial communities provide protection from disinfection procedures. This review collates the literature describing interactions between L. pneumophila and protozoan hosts in hospital and municipal potable water distribution systems. The effectiveness of currently available water disinfection protocols to control L. pneumophila and its protozoan hosts is explored. The studies identified in this systematic literature review demonstrated the failure of common disinfection procedures to achieve long term elimination of L. pneumophila and protozoan hosts from potable water. It has been demonstrated that protozoan hosts facilitate the intracellular replication and packaging of viable L. pneumophila in infectious vesicles; whereas, cyst-forming protozoans provide protection from prolonged environmental stress. Disinfection procedures and protozoan hosts also facilitate biogenesis of viable but non-culturable (VBNC) L. pneumophila which have been shown to be highly resistant to many water disinfection protocols. In conclusion, a better understanding of L. pneumophila-protozoan interactions and the structure of complex microbial biofilms is required for the improved management of L. pneumophila and the prevention of LD. Full article

(This article belongs to the Special Issue Legionella Contamination in Water Environment)

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17 pages, 1185 KiB

Open AccessFeature PaperEditor’s ChoiceReview

The Role of Long Noncoding RNAs in Human Papillomavirus-associated Pathogenesis

by Surendra Sharma and Karl Munger

Pathogens 2020, 9(4), 289; https://doi.org/10.3390/pathogens9040289 - 15 Apr 2020

Cited by 22 | Viewed by 5835

Abstract

Infections with high-risk human papillomaviruses cause ~5% of all human cancers. E6 and E7 are the only viral genes that are consistently expressed in cancers, and they are necessary for tumor initiation, progression, and maintenance. E6 and E7 encode small proteins that lack [...] Read more.

Infections with high-risk human papillomaviruses cause ~5% of all human cancers. E6 and E7 are the only viral genes that are consistently expressed in cancers, and they are necessary for tumor initiation, progression, and maintenance. E6 and E7 encode small proteins that lack intrinsic enzymatic activities and they function by binding to cellular regulatory molecules, thereby subverting normal cellular homeostasis. Much effort has focused on identifying protein targets of the E6 and E7 proteins, but it has been estimated that ~98% of the human transcriptome does not encode proteins. There is a growing interest in studying noncoding RNAs as biochemical targets and biological mediators of human papillomavirus (HPV) E6/E7 oncogenic activities. This review focuses on HPV E6/E7 targeting cellular long noncoding RNAs, a class of biologically versatile molecules that regulate almost every known biological process and how this may contribute to viral oncogenesis. Full article

(This article belongs to the Special Issue Viral-host interactions and determinants of human papillomavirus (HPV) life cycle and pathogenesis)

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16 pages, 2541 KiB

Open AccessEditor’s ChoiceArticle

First Whole Genome Sequence of Anaplasma platys, an Obligate Intracellular Rickettsial Pathogen of Dogs

by Alejandro Llanes and Sreekumari Rajeev

Pathogens 2020, 9(4), 277; https://doi.org/10.3390/pathogens9040277 - 10 Apr 2020

Cited by 10 | Viewed by 3771

Abstract

We have assembled the first genome draft of Anaplasma platys, an obligate intracellular rickettsia, and the only known bacterial pathogen infecting canine platelets. A. platys is a not-yet-cultivated bacterium that causes infectious cyclic canine thrombocytopenia, a potentially fatal disease in dogs. Despite [...] Read more.

We have assembled the first genome draft of Anaplasma platys, an obligate intracellular rickettsia, and the only known bacterial pathogen infecting canine platelets. A. platys is a not-yet-cultivated bacterium that causes infectious cyclic canine thrombocytopenia, a potentially fatal disease in dogs. Despite its global distribution and veterinary relevance, no genome sequence has been published so far for this pathogen. Here, we used a strategy based on metagenome assembly to generate a draft of the A. platys genome using the blood of an infected dog. The assembled draft is similar to other Anaplasma genomes in size, gene content, and synteny. Notable differences are the apparent absence of rbfA, a gene encoding a 30S ribosome-binding factor acting as a cold-shock protein, as well as two genes involved in biotin metabolism. We also observed differences associated with expanded gene families, including those encoding outer membrane proteins, a type IV secretion system, ankyrin repeat-containing proteins, and proteins with predicted intrinsically disordered regions. Several of these families have members highly divergent in sequence, likely to be associated with survival and interactions within the host and the vector. The sequence of the A. platys genome can benefit future studies regarding invasion, survival, and pathogenesis of Anaplasma species, while paving the way for the better design of treatment and prevention strategies against these neglected intracellular pathogens. Full article

(This article belongs to the Section Animal Pathogens)

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13 pages, 1770 KiB

Open AccessEditor’s ChoiceArticle

High-Resolution Melting (HRM) Curve Assay for the Identification of Eight Fusarium Species Causing Ear Rot in Maize

by Simon Schiwek, Lukas Beule, Maria Vinas, Annette Pfordt, Andreas von Tiedemann and Petr Karlovsky

Pathogens 2020, 9(4), 270; https://doi.org/10.3390/pathogens9040270 - 07 Apr 2020

Cited by 21 | Viewed by 4567

Abstract

Maize plants are often infected with fungal pathogens of the genus Fusarium. Taxonomic characterization of these species by microscopic examination of pure cultures or assignment to mating populations is time-consuming and requires specific expertise. Reliable taxonomic assignment may be strengthened by the [...] Read more.

Maize plants are often infected with fungal pathogens of the genus Fusarium. Taxonomic characterization of these species by microscopic examination of pure cultures or assignment to mating populations is time-consuming and requires specific expertise. Reliable taxonomic assignment may be strengthened by the analysis of DNA sequences. Species-specific PCR assays are available for most Fusarium pathogens, but the number of species that infect maize increases the labor and costs required for analysis. In this work, a diagnostic assay for major Fusarium pathogens of maize based on the analysis of melting curves of PCR amplicons was established. Short segments of genes RPB2 and TEF-1α, which have been widely used in molecular taxonomy of Fusarium, were amplified with universal primers in a real-time thermocycler and high-resolution melting (HRM) curves of the products were recorded. Among major Fusarium pathogens of maize ears, F. cerealis, F. culmorum, F. graminearum, F. equiseti, F. poae, F. temperatum, F. tricinctum, and F. verticillioides, all species except for the pair F. culmorum/F. graminearum could be distinguished by HRM analysis of a 304 bp segment of the RPB2 gene. The latter two species could be differentiated by HRM analysis of a 247 bp segment of the TEF-1α gene. The assay was validated with DNA extracted from pure cultures of fungal strains, successfully applied to total DNA extracted from infected maize ears and also to fungal mycelium that was added directly to the PCR master mix (“colony PCR”). HRM analysis thus offers a cost-efficient method suitable for the diagnosis of multiple fungal pathogens. Full article

(This article belongs to the Section Plant Pathogens)

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15 pages, 1281 KiB

Open AccessEditor’s ChoiceReview

A Systematic Review of Studies Published between 2016 and 2019 on the Effectiveness and Efficacy of Pneumococcal Vaccination on Pneumonia and Invasive Pneumococcal Disease in an Elderly Population

by Jacob Dag Berild, Brita Askeland Winje, Didrik Frimann Vestrheim, Hans-Christian Slotved, Palle Valentiner-Branth, Adam Roth and Jann Storsäter

Pathogens 2020, 9(4), 259; https://doi.org/10.3390/pathogens9040259 - 03 Apr 2020

Cited by 29 | Viewed by 5425

Abstract

Adult vaccination is high on the agenda in many countries. Two different vaccines are available for the prevention of pneumococcal disease in adults: a 23-valent polysaccharide vaccine (PPV23), and a 13-valent conjugated vaccine (PCV13). The objective of this review is to update the [...] Read more.

Adult vaccination is high on the agenda in many countries. Two different vaccines are available for the prevention of pneumococcal disease in adults: a 23-valent polysaccharide vaccine (PPV23), and a 13-valent conjugated vaccine (PCV13). The objective of this review is to update the evidence base for vaccine efficacy and effectiveness of PPV23 and PCV13 against invasive pneumococcal disease and pneumonia among an unselected elderly population. We systematically searched for clinical trials and observational studies published between January 1 2016 and April 17 2019 in Pubmed, Embase, Cinahl, Web of Science, Epistemonikos and Cochrane databases. Risk of bias was assessed using Cochrane Risk of Bias tool for and the Newcastle–Ottawa Scale. Results were stratified by vaccine type and outcome. We identified nine studies on PCV13 and six on PPV23. No new randomized clinical trials were identified. Due to different outcomes, it was not possible to do a meta-analysis. New high-quality observational studies indicate protective vaccine effectiveness for both vaccines against vaccine type pneumonia. Our estimates for the protective vaccine efficacy and effectiveness (VE) of PPV23 on pneumonia and pneumococcal pneumonia overlap with results from previously published reviews. Some of the results indicate that the effectiveness of the PPV23 is best in younger age groups, and that it decreases over time. Full article

(This article belongs to the Special Issue Development of Pneumococcal Vaccines for the World)

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28 pages, 1972 KiB

Open AccessEditor’s ChoiceReview

The Neuropathic Itch Caused by Pseudorabies Virus

by Kathlyn Laval and Lynn W. Enquist

Pathogens 2020, 9(4), 254; https://doi.org/10.3390/pathogens9040254 - 31 Mar 2020

Cited by 52 | Viewed by 8305

Abstract

Pseudorabies virus (PRV) is an alphaherpesvirus related to varicella-zoster virus (VZV) and herpes simplex virus type 1 (HSV1). PRV is the causative agent of Aujeskzy’s disease in swine. PRV infects mucosal epithelium and the peripheral nervous system (PNS) of its host where it [...] Read more.

Pseudorabies virus (PRV) is an alphaherpesvirus related to varicella-zoster virus (VZV) and herpes simplex virus type 1 (HSV1). PRV is the causative agent of Aujeskzy’s disease in swine. PRV infects mucosal epithelium and the peripheral nervous system (PNS) of its host where it can establish a quiescent, latent infection. While the natural host of PRV is the swine, a broad spectrum of mammals, including rodents, cats, dogs, and cattle can be infected. Since the nineteenth century, PRV infection is known to cause a severe acute neuropathy, the so called “mad itch” in non-natural hosts, but surprisingly not in swine. In the past, most scientific efforts have been directed to eradicating PRV from pig farms by the use of effective marker vaccines, but little attention has been given to the processes leading to the mad itch. The main objective of this review is to provide state-of-the-art information on the mechanisms governing PRV-induced neuropathic itch in non-natural hosts. We highlight similarities and key differences in the pathogenesis of PRV infections between non-natural hosts and pigs that might explain their distinctive clinical outcomes. Current knowledge on the neurobiology and possible explanations for the unstoppable itch experienced by PRV-infected animals is also reviewed. We summarize recent findings concerning PRV-induced neuroinflammatory responses in mice and address the relevance of this animal model to study other alphaherpesvirus-induced neuropathies, such as those observed for VZV infection. Full article

(This article belongs to the Special Issue Pseudorabies Virus Infections)

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15 pages, 2222 KiB

Open AccessEditor’s ChoiceArticle

Modeling of the HIV-1 Life Cycle in Productively Infected Cells to Predict Novel Therapeutic Targets

by Olga Shcherbatova, Dmitry Grebennikov, Igor Sazonov, Andreas Meyerhans and Gennady Bocharov

Pathogens 2020, 9(4), 255; https://doi.org/10.3390/pathogens9040255 - 31 Mar 2020

Cited by 19 | Viewed by 5324

Abstract

There are many studies that model the within-host population dynamics of Human Immunodeficiency Virus Type 1 (HIV-1) infection. However, the within-infected-cell replication of HIV-1 remains to be not comprehensively addressed. There exist rather few quantitative models describing the regulation of the HIV-1 life [...] Read more.

There are many studies that model the within-host population dynamics of Human Immunodeficiency Virus Type 1 (HIV-1) infection. However, the within-infected-cell replication of HIV-1 remains to be not comprehensively addressed. There exist rather few quantitative models describing the regulation of the HIV-1 life cycle at the intracellular level. In treatment of HIV-1 infection, there remain issues related to side-effects and drug-resistance that require further search “...for new and better drugs, ideally targeting multiple independent steps in the HIV-1 replication cycle” (as highlighted recently by Tedbury & Freed, The Future of HIV-1 Therapeutics, 2015). High-resolution mathematical models of HIV-1 growth in infected cells provide an additional analytical tool in identifying novel drug targets. We formulate a high-dimensional model describing the biochemical reactions underlying the replication of HIV-1 in target cells. The model considers a nonlinear regulation of the transcription of HIV-1 mediated by Tat and the Rev-dependent transport of fully spliced and singly spliced transcripts from the nucleus to the cytoplasm. The model is calibrated using available information on the kinetics of various stages of HIV-1 replication. The sensitivity analysis of the model is performed to rank the biochemical processes of HIV-1 replication with respect to their impact on the net production of virions by one actively infected cell. The ranking of the sensitivity factors provides a quantitative basis for identifying novel targets for antiviral therapy. Our analysis suggests that HIV-1 assembly depending on Gag and Tat-Rev regulation of transcription and mRNA distribution present two most critical stages in HIV-1 replication that can be targeted to effectively control virus production. These processes are not covered by current antiretroviral treatments. Full article

(This article belongs to the Special Issue Modeling Virus Dynamics and Evolution)

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12 pages, 1706 KiB

Open AccessEditor’s ChoiceArticle

In Vitro Anti-NTHi Activity of Haemophilin-Producing Strains of Haemophilus haemolyticus

by Brianna Atto, Roger Latham, Dale Kunde, David A Gell and Stephen Tristram

Pathogens 2020, 9(4), 243; https://doi.org/10.3390/pathogens9040243 - 25 Mar 2020

Cited by 7 | Viewed by 2666

Abstract

Nontypeable Haemophilus influenzae (NTHi) is a leading causative organism of opportunistic respiratory tract infections. However, there are currently no effective vaccination strategies, and existing treatments are compromised by antibiotic resistance. We previously characterized Haemophilus haemolyticus (Hh) strains capable of producing haemophilin (HPL), a [...] Read more.

Nontypeable Haemophilus influenzae (NTHi) is a leading causative organism of opportunistic respiratory tract infections. However, there are currently no effective vaccination strategies, and existing treatments are compromised by antibiotic resistance. We previously characterized Haemophilus haemolyticus (Hh) strains capable of producing haemophilin (HPL), a heme-binding protein that restricts NTHi growth by limiting its access to an essential growth factor, heme. Thus, these strains may have utility as a probiotic therapy against NTHi infection by limiting colonization, migration and subsequent infection in susceptible individuals. Here, we assess the preliminary feasibility of this approach by direct in vitro competition assays between NTHi and Hh strains with varying capacity to produce HPL. Subsequent changes in NTHi growth rate and fitness, in conjunction with HPL expression analysis, were employed to assess the NTHi-inhibitory capacity of Hh strains. HPL-producing strains of Hh not only outcompeted NTHi during short-term and extended co-culture, but also demonstrated a growth advantage compared with Hh strains unable to produce the protein. Additionally, HPL expression levels during competition correlated with the NTHi-inhibitory phenotype. HPL-producing strains of Hh demonstrate significant probiotic potential against NTHi colonization in the upper respiratory tract, however, further investigations are warranted to demonstrate a range of other characteristics that would support the eventual development of a probiotic. Full article

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12 pages, 2796 KiB

Open AccessEditor’s ChoiceArticle

Evolutionary Trajectory for the Emergence of Novel Coronavirus SARS-CoV-2

by Saif ur Rehman, Laiba Shafique, Awais Ihsan and Qingyou Liu

Pathogens 2020, 9(3), 240; https://doi.org/10.3390/pathogens9030240 - 23 Mar 2020

Cited by 152 | Viewed by 26438

Abstract

Over the last two decades, the world experienced three outbreaks of coronaviruses with elevated morbidity rates. Currently, the global community is facing emerging virus SARS-CoV-2 belonging to Betacoronavirus, which appears to be more transmissible but less deadly than SARS-CoV. The current study [...] Read more.

Over the last two decades, the world experienced three outbreaks of coronaviruses with elevated morbidity rates. Currently, the global community is facing emerging virus SARS-CoV-2 belonging to Betacoronavirus, which appears to be more transmissible but less deadly than SARS-CoV. The current study aimed to track the evolutionary ancestors and different evolutionary strategies that were genetically adapted by SARS-CoV-2. Our whole-genome analysis revealed that SARS-CoV-2 was the descendant of Bat SARS/SARS-like CoVs and bats served as a natural reservoir. SARS-CoV-2 used mutations and recombination as crucial strategies in different genomic regions including the envelop, membrane, nucleocapsid, and spike glycoproteins to become a novel infectious agent. We confirmed that mutations in different genomic regions of SARS-CoV-2 have specific influence on virus reproductive adaptability, allowing for genotype adjustment and adaptations in rapidly changing environments. Moreover, for the first time we identified nine putative recombination patterns in SARS-CoV-2, which encompass spike glycoprotein, RdRp, helicase and ORF3a. Six recombination regions were spotted in the S gene and are undoubtedly important for evolutionary survival, meanwhile this permitted the virus to modify superficial antigenicity to find a way from immune reconnaissance in animals and adapt to a human host. With these combined natural selected strategies, SARS-CoV-2 emerged as a novel virus in human society. Full article

(This article belongs to the Section Animal Pathogens)

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