Viruses

13 pages, 1641 KiB

Open AccessArticle

Prevalence and Clinical Impact of Coinfection in Patients with Coronavirus Disease 2019 in Korea

by Seri Jeong, Nuri Lee, Yeeun Park, Jaehong Kim, Kibum Jeon, Min-Jeong Park and Wonkeun Song

Viruses 2022, 14(2), 446; https://doi.org/10.3390/v14020446 - 21 Feb 2022

Cited by 13 | Viewed by 2482

Abstract

Coinfection rates with other pathogens in coronavirus disease 2019 (COVID-19) varied during the pandemic. We assessed the latest prevalence of coinfection with viruses, bacteria, and fungi in COVID-19 patients for more than one year and its impact on mortality. A total of 436 [...] Read more.

Coinfection rates with other pathogens in coronavirus disease 2019 (COVID-19) varied during the pandemic. We assessed the latest prevalence of coinfection with viruses, bacteria, and fungi in COVID-19 patients for more than one year and its impact on mortality. A total of 436 samples were collected between August 2020 and October 2021. Multiplex real-time PCR, culture, and antimicrobial susceptibility testing were performed to detect pathogens. The coinfection rate of respiratory viruses in COVID-19 patients was 1.4%. Meanwhile, the rates of bacteria and fungi were 52.6% and 10.5% in hospitalized COVID-19 patients, respectively. Respiratory syncytial virus, rhinovirus, Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans were the most commonly detected pathogens. Ninety percent of isolated A. baumannii was non-susceptible to carbapenem. Based on a multivariate analysis, coinfection (odds ratio [OR] = 6.095), older age (OR = 1.089), and elevated lactate dehydrogenase (OR = 1.006) were risk factors for mortality as a critical outcome. In particular, coinfection with bacteria (OR = 11.250), resistant pathogens (OR = 11.667), and infection with multiple pathogens (OR = 10.667) were significantly related to death. Screening and monitoring of coinfection in COVID-19 patients, especially for hospitalized patients during the pandemic, are beneficial for better management and survival. Full article

(This article belongs to the Special Issue Respiratory Viral Coinfection)

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15 pages, 1412 KiB

Open AccessReview

Crosstalk between Hepatitis B Virus and the 3D Genome Structure

by João Diogo Dias, Nazim Sarica, Axel Cournac, Romain Koszul and Christine Neuveut

Viruses 2022, 14(2), 445; https://doi.org/10.3390/v14020445 - 21 Feb 2022

Cited by 3 | Viewed by 2819

Abstract

Viruses that transcribe their DNA within the nucleus have to adapt to the existing cellular mechanisms that govern transcriptional regulation. Recent technological breakthroughs have highlighted the highly hierarchical organization of the cellular genome and its role in the regulation of gene expression. This [...] Read more.

Viruses that transcribe their DNA within the nucleus have to adapt to the existing cellular mechanisms that govern transcriptional regulation. Recent technological breakthroughs have highlighted the highly hierarchical organization of the cellular genome and its role in the regulation of gene expression. This review provides an updated overview on the current knowledge on how the hepatitis B virus interacts with the cellular 3D genome and its consequences on viral and cellular gene expression. We also briefly discuss the strategies developed by other DNA viruses to co-opt and sometimes subvert cellular genome spatial organization. Full article

(This article belongs to the Special Issue Epigenetic Regulation of cccDNA Functions and HBV Replication)

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7 pages, 487 KiB

Open AccessCommunication

Interferon-β Suppresses Transcriptionally Active Parvovirus B19 Infection in Viral Cardiomyopathy: A Subgroup Analysis of the BICC-Trial

by Heinz-Peter Schultheiss, Claus-Thomas Bock, Ganna Aleshcheva, Christian Baumeier, Wolfgang Poller and Felicitas Escher

Viruses 2022, 14(2), 444; https://doi.org/10.3390/v14020444 - 21 Feb 2022

Cited by 6 | Viewed by 1921

Abstract

Human parvovirus B19 (B19V) is the predominant virus currently detected in endomyocardial biopsies (EMBs). Recent findings indicate that, specifically, transcriptionally active B19V with detectable viral RNA is of prognostic relevance in inflammatory viral cardiomyopathy. We aimed to evaluate B19V replicative status (viral RNA) [...] Read more.

Human parvovirus B19 (B19V) is the predominant virus currently detected in endomyocardial biopsies (EMBs). Recent findings indicate that, specifically, transcriptionally active B19V with detectable viral RNA is of prognostic relevance in inflammatory viral cardiomyopathy. We aimed to evaluate B19V replicative status (viral RNA) and beneficial effects in a sub-collective of the prospective randomized placebo-controlled phase II multi-center BICC-Trial (Betaferon In Chronic Viral Cardiomyopathy) after interferon beta-1b (IFN-β) treatment. EMBs of n = 64 patients with B19V mono-infected tissue were retrospectively analyzed. Viral RNA could be detected in n = 18/64 (28.1%) of B19V DNA positive samples (mean age 51.7 years, 12 male), of whom n = 13 had been treated with IFN-ß. Five patients had received placebo. PCR analysis confirmed in follow-up that EMBs significantly reduced viral RNA loads in n = 11/13 (84.6%) of IFN-ß treated patients (p = 0.001), independently from the IFN-ß dose, in contrast to the placebo group, where viral RNA load was not affected or even increased. Consequently, a significant improvement of left ventricular ejection fraction (LVEF) after treatment with IFN-ß was observed (LVEF mean baseline 51.6 ± 14.1% vs. follow-up 61.0 ± 17.5%, p = 0.03). In contrast, in the placebo group, worsening of LVEF was evaluated in n = 4/5 (80.0%) of patients. We could show for the first-time the beneficial effects from treatment with IFN-ß, suppressing B19V viral RNA and improving the hemodynamic course. Our results need further verification in a larger prospective randomized controlled trial. Full article

(This article belongs to the Section Human Virology and Viral Diseases)

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15 pages, 5202 KiB

Open AccessArticle

Collection of Monoclonal Antibodies Targeting SARS-CoV-2 Proteins

by Marina Pribanić Matešić, Paola Kučan Brlić, Tihana Lenac Roviš, Željka Mačak Šafranko, Abigael Eva Chaouat, Karmela Miklić, Suzana Malić, Nina Ivanković, Maren Schubert, Federico Bertoglio, Alemka Markotić, Ofer Mandelboim, Stipan Jonjić and Ilija Brizić

Viruses 2022, 14(2), 443; https://doi.org/10.3390/v14020443 - 21 Feb 2022

Cited by 3 | Viewed by 3076

Abstract

In early 2020, the COVID-19 pandemic sparked a global crisis that continues to pose a serious threat to human health and the economy. Further advancement in research is necessary and requires the availability of quality molecular tools, including monoclonal antibodies. Here, we present [...] Read more.

In early 2020, the COVID-19 pandemic sparked a global crisis that continues to pose a serious threat to human health and the economy. Further advancement in research is necessary and requires the availability of quality molecular tools, including monoclonal antibodies. Here, we present the development and characterization of a collection of over 40 new monoclonal antibodies directed against different SARS-CoV-2 proteins. Recombinant SARS-CoV-2 proteins were expressed, purified, and used as immunogens. Upon development of specific hybridomas, the obtained monoclonal antibody (mAb) clones were tested for binding to recombinant proteins and infected cells. We generated mAbs against structural proteins, the Spike and Nucleocapsid protein, several non-structural proteins (nsp1, nsp7, nsp8, nsp9, nsp10, nsp16) and accessory factors (ORF3a, ORF9b) applicable in flow cytometry, immunofluorescence, or Western blot. Our collection of mAbs provides a set of novel, highly specific tools that will allow a comprehensive analysis of the viral proteome, which will allow further understanding of SARS-CoV-2 pathogenesis and the design of therapeutic strategies. Full article

(This article belongs to the Special Issue State-of-the-Art Virology Research in Croatia)

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20 pages, 1252 KiB

Open AccessReview

Schlafens Can Put Viruses to Sleep

by Eui Tae Kim and Matthew D. Weitzman

Viruses 2022, 14(2), 442; https://doi.org/10.3390/v14020442 - 21 Feb 2022

Cited by 8 | Viewed by 4348

Abstract

The Schlafen gene family encodes for proteins involved in various biological tasks, including cell proliferation, differentiation, and T cell development. Schlafens were initially discovered in mice, and have been studied in the context of cancer biology, as well as their role in protecting [...] Read more.

The Schlafen gene family encodes for proteins involved in various biological tasks, including cell proliferation, differentiation, and T cell development. Schlafens were initially discovered in mice, and have been studied in the context of cancer biology, as well as their role in protecting cells during viral infection. This protein family provides antiviral barriers via direct and indirect effects on virus infection. Schlafens can inhibit the replication of viruses with both RNA and DNA genomes. In this review, we summarize the cellular functions and the emerging relationship between Schlafens and innate immunity. We also discuss the functions and distinctions of this emerging family of proteins as host restriction factors against viral infection. Further research into Schlafen protein function will provide insight into their mechanisms that contribute to intrinsic and innate host immunity. Full article

(This article belongs to the Special Issue Interaction between Virus and Host Innate Immune Systems)

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10 pages, 813 KiB

Open AccessArticle

Naïve Human Macrophages Are Refractory to SARS-CoV-2 Infection and Exhibit a Modest Inflammatory Response Early in Infection

by Ziyun Zhang, Rebecca Penn, Wendy S. Barclay and Efstathios S. Giotis

Viruses 2022, 14(2), 441; https://doi.org/10.3390/v14020441 - 21 Feb 2022

Cited by 9 | Viewed by 3271

Abstract

Involvement of macrophages in the SARS-CoV-2-associated cytokine storm, the excessive secretion of inflammatory/anti-viral factors leading to the acute respiratory distress syndrome (ARDS) in COVID-19 patients, is unclear. In this study, we sought to characterize the interplay between the virus and primary human monocyte-derived [...] Read more.

Involvement of macrophages in the SARS-CoV-2-associated cytokine storm, the excessive secretion of inflammatory/anti-viral factors leading to the acute respiratory distress syndrome (ARDS) in COVID-19 patients, is unclear. In this study, we sought to characterize the interplay between the virus and primary human monocyte-derived macrophages (MDM). MDM were stimulated with recombinant IFN-α and/or infected with either live or UV-inactivated SARS-CoV-2 or with two reassortant influenza viruses containing external genes from the H1N1 PR8 strain and heterologous internal genes from a highly pathogenic avian H5N1 or a low pathogenic human seasonal H1N1 strain. Virus replication was monitored by qRT-PCR for the E viral gene for SARS-CoV-2 or M gene for influenza and TCID₅₀ or plaque assay, and cytokine levels were assessed semiquantitatively with qRT-PCR and a proteome cytokine array. We report that MDM are not susceptible to SARS-CoV-2 whereas both influenza viruses replicated in MDM, albeit abortively. We observed a modest cytokine response in SARS-CoV-2 exposed MDM with notable absence of IFN-β induction, which was instead strongly induced by the influenza viruses. Pre-treatment of MDM with IFN-α enhanced proinflammatory cytokine expression upon exposure to virus. Together, the findings concur that the hyperinflammation observed in SARS-CoV-2 infection is not driven by macrophages. Full article

(This article belongs to the Special Issue Viral Strategies of Immune Evasion)

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23 pages, 9488 KiB

Open AccessArticle

Genomic Bootstrap Barcodes and Their Application to Study the Evolution of Sarbecoviruses

by Alexandre Hassanin, Opale Rambaud and Dylan Klein

Viruses 2022, 14(2), 440; https://doi.org/10.3390/v14020440 - 21 Feb 2022

Cited by 7 | Viewed by 2366

Abstract

Recombination creates mosaic genomes containing regions with mixed ancestry, and the accumulation of such events over time can complicate greatly many aspects of evolutionary inference. Here, we developed a sliding window bootstrap (SWB) method to generate genomic bootstrap (GB) barcodes to highlight the [...] Read more.

Recombination creates mosaic genomes containing regions with mixed ancestry, and the accumulation of such events over time can complicate greatly many aspects of evolutionary inference. Here, we developed a sliding window bootstrap (SWB) method to generate genomic bootstrap (GB) barcodes to highlight the regions supporting phylogenetic relationships. The method was applied to an alignment of 56 sarbecoviruses, including SARS-CoV and SARS-CoV-2, responsible for the SARS epidemic and COVID-19 pandemic, respectively. The SWB analyses were also used to construct a consensus tree showing the most reliable relationships and better interpret hidden phylogenetic signals. Our results revealed that most relationships were supported by just a few genomic regions and confirmed that three divergent lineages could be found in bats from Yunnan: SCoVrC, which groups SARS-CoV related coronaviruses from China; SCoV2rC, which includes SARS-CoV-2 related coronaviruses from Southeast Asia and Yunnan; and YunSar, which contains a few highly divergent viruses recently described in Yunnan. The GB barcodes showed evidence for ancient recombination between SCoV2rC and YunSar genomes, as well as more recent recombination events between SCoVrC and SCoV2rC genomes. The recombination and phylogeographic patterns suggest a strong host-dependent selection of the viral RNA-dependent RNA polymerase. In addition, SARS-CoV-2 appears as a mosaic genome composed of regions sharing recent ancestry with three bat SCoV2rCs from Yunnan (RmYN02, RpYN06, and RaTG13) or related to more ancient ancestors in bats from Yunnan and Southeast Asia. Finally, our results suggest that viral circular RNAs may be key molecules for the mechanism of recombination. Full article

(This article belongs to the Section General Virology)

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10 pages, 546 KiB

Open AccessArticle

Incidence and Risk Factors of Reinfection with HCV after Treatment in People Living with HIV

by Chien-Yu Cheng, Shin-Yen Ku, Yi-Chun Lin, Cheng-Pin Chen, Shu-Hsing Cheng and I-Feng Lin

Viruses 2022, 14(2), 439; https://doi.org/10.3390/v14020439 - 21 Feb 2022

Cited by 6 | Viewed by 2069

Abstract

Infection with hepatitis C virus (HCV) does not induce protective immunity, and re-exposure to HCV can reinfect the population engaging in high-risk behavior. An increasing incidence of acute hepatitis C infection in people living with HIV (PLWH) has been described in recent years. [...] Read more.

Infection with hepatitis C virus (HCV) does not induce protective immunity, and re-exposure to HCV can reinfect the population engaging in high-risk behavior. An increasing incidence of acute hepatitis C infection in people living with HIV (PLWH) has been described in recent years. This retrospective cohort study was conducted in PLWH who completed HCV therapy between June 2009 and June 2020 at an HIV care hospital, to analyze their basic characteristics and risky behavior. Of 2419 patients, 639 were diagnosed with HCV infection and 516 completed the HCV therapy with a sustained virologic response. In total, 59 patients (11.4%) were reinfected with acute hepatitis C, and the median time to reinfection was 85.3 weeks (IQR: 57–150). The incidence of reinfection was 6.7 cases/100 person-years. The factors associated with reinfection were being male (AHR, 8.02; 95% CI 1.08–59.49), DAA (direct-acting antiviral) treatment (AHR, 2.23; 95% CI 1.04–4.79), liver cirrhosis (AHR, 3.94; 95% CI 1.09–14.22), heroin dependency (AHR: 7.41; 95% CI 3.37–14.3), and HIV viral loads <50 copies/mL at the follow-up (AHR: 0.47, 95% CI 0.24–0.93) in the subgroup of people who inject drugs (PWID). Amphetamine abuse (AHR: 20.17; 95% CI 2.36–172.52) was the dominant factor in the subgroup of men who have sex with men (MSM). Our study suggests that education and behavioral interventions are needed in this population to prevent reinfection. Full article

(This article belongs to the Topic Infectious Diseases)

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23 pages, 20381 KiB

Open AccessReview

Viral Aggregation: The Knowns and Unknowns

by Swechchha Pradhan, Arvind Varsani, Chloe Leff, Carter J. Swanson and Rizal F. Hariadi

Viruses 2022, 14(2), 438; https://doi.org/10.3390/v14020438 - 21 Feb 2022

Cited by 18 | Viewed by 5932

Abstract

Viral aggregation is a complex and pervasive phenomenon affecting many viral families. An increasing number of studies have indicated that it can modulate critical parameters surrounding viral infections, and yet its role in viral infectivity, pathogenesis, and evolution is just beginning to be [...] Read more.

Viral aggregation is a complex and pervasive phenomenon affecting many viral families. An increasing number of studies have indicated that it can modulate critical parameters surrounding viral infections, and yet its role in viral infectivity, pathogenesis, and evolution is just beginning to be appreciated. Aggregation likely promotes viral infection by increasing the cellular multiplicity of infection (MOI), which can help overcome stochastic failures of viral infection and genetic defects and subsequently modulate their fitness, virulence, and host responses. Conversely, aggregation can limit the dispersal of viral particles and hinder the early stages of establishing a successful infection. The cost–benefit of viral aggregation seems to vary not only depending on the viral species and aggregating factors but also on the spatiotemporal context of the viral life cycle. Here, we review the knowns of viral aggregation by focusing on studies with direct observations of viral aggregation and mechanistic studies of the aggregation process. Next, we chart the unknowns and discuss the biological implications of viral aggregation in their infection cycle. We conclude with a perspective on harnessing the therapeutic potential of this phenomenon and highlight several challenging questions that warrant further research for this field to advance. Full article

(This article belongs to the Special Issue Physical Virology - Viruses at Multiple Levels of Complexity)

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14 pages, 503 KiB

Open AccessReview

Application of the CRISPR/Cas9 System to Study Regulation Pathways of the Cellular Immune Response to Influenza Virus

by Daria Prokhorova, Natalya Zhukova (Eschenko), Anna Lemza, Mariia Sergeeva, Rinat Amirkhanov and Grigory Stepanov

Viruses 2022, 14(2), 437; https://doi.org/10.3390/v14020437 - 21 Feb 2022

Cited by 3 | Viewed by 3265

Abstract

Influenza A virus (IAV) causes a respiratory infection that affects millions of people of different age groups and can lead to acute respiratory distress syndrome. Currently, host genes, receptors, and other cellular components critical for IAV replication are actively studied. One of the [...] Read more.

Influenza A virus (IAV) causes a respiratory infection that affects millions of people of different age groups and can lead to acute respiratory distress syndrome. Currently, host genes, receptors, and other cellular components critical for IAV replication are actively studied. One of the most convenient and accessible genome-editing tools to facilitate these studies is the CRISPR/Cas9 system. This tool allows for regulating the expression of both viral and host cell genes to enhance or impair viral entry and replication. This review considers the effect of the genome editing system on specific target genes in cells (human and chicken) in terms of subsequent changes in the influenza virus life cycle and the efficiency of virus particle production. Full article

(This article belongs to the Special Issue CRISPR/Cas in Viral Research)

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14 pages, 1901 KiB

Open AccessArticle

V5 and GFP Tagging of Viral Gene pp38 of Marek’s Disease Vaccine Strain CVI988 Using CRISPR/Cas9 Editing

by Weicheng Li, Yaoyao Zhang, Katy Moffat, Venugopal Nair and Yongxiu Yao

Viruses 2022, 14(2), 436; https://doi.org/10.3390/v14020436 - 21 Feb 2022

Viewed by 2708

Abstract

Marek’s disease virus (MDV) is a member of alphaherpesviruses associated with Marek’s disease, a highly contagious neoplastic disease in chickens. The availability of the complete sequence of the viral genome allowed for the identification of major genes associated with pathogenicity using different techniques, [...] Read more.

Marek’s disease virus (MDV) is a member of alphaherpesviruses associated with Marek’s disease, a highly contagious neoplastic disease in chickens. The availability of the complete sequence of the viral genome allowed for the identification of major genes associated with pathogenicity using different techniques, such as bacterial artificial chromosome (BAC) mutagenesis and the recent powerful clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-based editing system. Thus far, most studies on MDV genome editing using the CRISPR/Cas9 system have focused on gene deletion. However, analysis of the expression and interactions of the viral proteins during virus replication in infected cells and tumor cells is also important for studying its role in MDV pathogenesis. The unavailability of antibodies against most of the MDV proteins has hindered the progress in such studies. This prompted us to develop pipelines to tag MDV genes as an alternative method for this purpose. Here we describe the application of CRISPR/Cas9 gene-editing approaches to tag the phosphoprotein 38 (pp38) gene of the MDV vaccine strain CVI988 with both V5 and green fluorescent protein (GFP). This rapid and efficient viral-gene-tagging technique can overcome the shortage of specific antibodies and speed up the MDV gene function studies significantly, leading to a better understanding of the molecular mechanisms of MDV pathogenesis. Full article

(This article belongs to the Special Issue Animal Herpesviruses Pathogenesis and Immunity)

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11 pages, 275 KiB

Open AccessReview

Adaptive Evolution as a Driving Force of the Emergence and Re-Emergence of Mosquito-Borne Viral Diseases

by Xi Yu and Gong Cheng

Viruses 2022, 14(2), 435; https://doi.org/10.3390/v14020435 - 21 Feb 2022

Cited by 9 | Viewed by 3163

Abstract

Emerging and re-emerging mosquito-borne viral diseases impose a significant burden on global public health. The most common mosquito-borne viruses causing recent epidemics include flaviviruses in the family Flaviviridae, including Dengue virus (DENV), Zika virus (ZIKV), Japanese encephalitis virus (JEV) and West Nile [...] Read more.

Emerging and re-emerging mosquito-borne viral diseases impose a significant burden on global public health. The most common mosquito-borne viruses causing recent epidemics include flaviviruses in the family Flaviviridae, including Dengue virus (DENV), Zika virus (ZIKV), Japanese encephalitis virus (JEV) and West Nile virus (WNV) and Togaviridae viruses, such as chikungunya virus (CHIKV). Several factors may have contributed to the recent re-emergence and spread of mosquito-borne viral diseases. Among these important causes are the evolution of mosquito-borne viruses and the genetic mutations that make them more adaptive and virulent, leading to widespread epidemics. RNA viruses tend to acquire genetic diversity due to error-prone RNA-dependent RNA polymerases, thus promoting high mutation rates that support adaptation to environmental changes or host immunity. In this review, we discuss recent findings on the adaptive evolution of mosquito-borne viruses and their impact on viral infectivity, pathogenicity, vector fitness, transmissibility, epidemic potential and disease emergence. Full article

(This article belongs to the Section Insect Viruses)

12 pages, 1150 KiB

Open AccessReview

Current Trend in Antiviral Therapy for Chronic Hepatitis B

by Rong-Nan Chien and Yun-Fan Liaw

Viruses 2022, 14(2), 434; https://doi.org/10.3390/v14020434 - 21 Feb 2022

Cited by 53 | Viewed by 7076

Abstract

Since active hepatitis B virus (HBV) replication is the key driver of hepatic necroinflammation and disease progression, the treatment aim of chronic hepatitis B (CHB) is to suppress HBV replication permanently to prevent hepatic decompensation, liver cirrhosis and/or hepatocellular carcinoma and prolong survival. [...] Read more.

Since active hepatitis B virus (HBV) replication is the key driver of hepatic necroinflammation and disease progression, the treatment aim of chronic hepatitis B (CHB) is to suppress HBV replication permanently to prevent hepatic decompensation, liver cirrhosis and/or hepatocellular carcinoma and prolong survival. Currently, pegylated interferon (Peg-IFN), entecavir (ETV), tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) are the first-line drugs of choice. Peg-IFN therapy has been used rarely due to its subcutaneous injection and significant side effect profile. Once daily oral ETV, TDF and TAF can suppress HBV DNA profoundly but have no direct action on cccDNA of the HBV-infected hepatocytes, hence continuing long-term therapy is usually needed to maintain HBV suppression, but the ultimate goal of HBsAg loss was rarely achieved (10 year 2%). In addition, long-term NUC therapy comes with several concerns such as increasing cost, medication adherence and loss-to-follow-up. Studies, mainly from Taiwan, have shown that finite NUCs therapy of two to three years in HBeAg-negative patients is feasible, safe and has a great benefit of much increasing HBsAg loss rate up to 30%/5 year. These have led an emerging paradigm shift to finite NUC therapy in HBeAg-negative patients globally. However, off-NUC relapse with hepatitis B flares may occur and have a risk of decompensation or even life-threatening outcomes. Therefore, proper monitoring, assessment, and retreatment decisions are crucial to ensure safety. Ideally, retreatment should be not too late to ensure safety and also not too early to allow further immune response for further HBsAg decline toward HBsAg loss. Assessment using combined HBsAg/ALT kinetics during hepatitis flare is better than biochemical markers alone to make a right retreatment decision. The strategy of finite NUC therapy has set a benchmark of high HBsAg loss rate to be achieved by the new anti-HBV drugs which are under preclinical or early phase study. Full article

(This article belongs to the Special Issue State-of-the-Art Chronic Hepatitis Viruses Research in Asia)

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17 pages, 2398 KiB

Open AccessArticle

A Novel Wide-Range Freshwater Cyanophage MinS1 Infecting the Harmful Cyanobacterium Microcystis aeruginosa

by Shanshan Zhang, Xiaoqi He, Lei Cao, Yigang Tong, Baohua Zhao and Wenlin An

Viruses 2022, 14(2), 433; https://doi.org/10.3390/v14020433 - 20 Feb 2022

Cited by 8 | Viewed by 2690

Abstract

Microcystis aeruginosa, as one of the major players in algal bloom, produces microcystins, which are strongly hepatotoxic, endangering human health and damaging the ecological environment. Biological control of the overgrowth of Microcystis with cyanophage has been proposed to be a promising solution [...] Read more.

Microcystis aeruginosa, as one of the major players in algal bloom, produces microcystins, which are strongly hepatotoxic, endangering human health and damaging the ecological environment. Biological control of the overgrowth of Microcystis with cyanophage has been proposed to be a promising solution for algal bloom. In this study, a novel strain of Microcystis cyanophage, MinS1, was isolated. MinS1 contains an icosahedral head approximately 54 nm in diameter and a 260 nm-long non-contractile tail. The phage genome consists of a linear, double-stranded 49,966 bp DNA molecule, which shares very low homology with known phages in the NCBI database (only 1% of the genome showed weak homology with known phages when analyzed by megablast). The phage contains 75 ORFs, of which 23 ORFs were predicted to code for proteins of known function, 39 ORFs were predicted to code for proteins of unknown function, and 13 ORFs showed no similarity to any protein sequences. Transmission electron microscopy and phylogenetic analysis showed that MinS1 belongs to the family Siphoviridae. Various experiments confirmed that the phage could infect several different orders of cyanobacteria, including Chroococcales, Nostocales, Oscillatoriales, Hormogonales, and Synechococcales, indicating that it has a very broad host range. In addition, MinS1 has no known antibiotic tolerance genes, virulence genes, and tRNAs, and it is tolerant to temperature, pH, UV, and salinity, suggesting that MinS1 has good potential for application as a biological control agent against cyanobacterial blooms. This study expands the diversity and knowledge of cyanophages, and it provides useful information for the development of novel prevention and control measures against cyanobacterial blooms. Full article

(This article belongs to the Section Bacterial Viruses)

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18 pages, 923 KiB

Open AccessReview

RNAi-Based Antiviral Innate Immunity in Plants

by Liying Jin, Mengna Chen, Meiqin Xiang and Zhongxin Guo

Viruses 2022, 14(2), 432; https://doi.org/10.3390/v14020432 - 20 Feb 2022

Cited by 14 | Viewed by 3613

Abstract

Multiple antiviral immunities were developed to defend against viral infection in hosts. RNA interference (RNAi)-based antiviral innate immunity is evolutionarily conserved in eukaryotes and plays a vital role against all types of viruses. During the arms race between the host and virus, many [...] Read more.

Multiple antiviral immunities were developed to defend against viral infection in hosts. RNA interference (RNAi)-based antiviral innate immunity is evolutionarily conserved in eukaryotes and plays a vital role against all types of viruses. During the arms race between the host and virus, many viruses evolve viral suppressors of RNA silencing (VSRs) to inhibit antiviral innate immunity. Here, we reviewed the mechanism at different stages in RNAi-based antiviral innate immunity in plants and the counteractions of various VSRs, mainly upon infection of RNA viruses in model plant Arabidopsis. Some critical challenges in the field were also proposed, and we think that further elucidating conserved antiviral innate immunity may convey a broad spectrum of antiviral strategies to prevent viral diseases in the future. Full article

(This article belongs to the Special Issue State-of-the-Art Plant Virus Research in China)

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21 pages, 5506 KiB

Open AccessArticle

Vaccinia Virus Arrests and Shifts the Cell Cycle

by Caroline K. Martin, Jerzy Samolej, Annabel T. Olson, Cosetta Bertoli, Matthew S. Wiebe, Robertus A. M. de Bruin and Jason Mercer

Viruses 2022, 14(2), 431; https://doi.org/10.3390/v14020431 - 19 Feb 2022

Cited by 2 | Viewed by 3045

Abstract

Modulation of the host cell cycle is a common strategy used by viruses to create a pro-replicative environment. To facilitate viral genome replication, vaccinia virus (VACV) has been reported to alter cell cycle regulation and trigger the host cell DNA damage response. However, [...] Read more.

Modulation of the host cell cycle is a common strategy used by viruses to create a pro-replicative environment. To facilitate viral genome replication, vaccinia virus (VACV) has been reported to alter cell cycle regulation and trigger the host cell DNA damage response. However, the cellular factors and viral effectors that mediate these changes remain unknown. Here, we set out to investigate the effect of VACV infection on cell proliferation and host cell cycle progression. Using a subset of VACV mutants, we characterise the stage of infection required for inhibition of cell proliferation and define the viral effectors required to dysregulate the host cell cycle. Consistent with previous studies, we show that VACV inhibits and subsequently shifts the host cell cycle. We demonstrate that these two phenomena are independent of one another, with viral early genes being responsible for cell cycle inhibition, and post-replicative viral gene(s) responsible for the cell cycle shift. Extending previous findings, we show that the viral kinase F10 is required to activate the DNA damage checkpoint and that the viral B1 kinase and/or B12 pseudokinase mediate degradation of checkpoint effectors p53 and p21 during infection. We conclude that VACV modulates host cell proliferation and host cell cycle progression through temporal expression of multiple VACV effector proteins. (209/200.) Full article

(This article belongs to the Special Issue Poxvirus)

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20 pages, 4061 KiB

Open AccessArticle

Transkingdom Analysis of the Female Reproductive Tract Reveals Bacteriophages form Communities

by Ferralita S. Madere, Michael Sohn, Angelina K. Winbush, Breóna Barr, Alex Grier, Cal Palumbo, James Java, Tracy Meiring, Anna-Lise Williamson, Linda-Gail Bekker, David H. Adler and Cynthia L. Monaco

Viruses 2022, 14(2), 430; https://doi.org/10.3390/v14020430 - 19 Feb 2022

Cited by 8 | Viewed by 2734

Abstract

The female reproductive tract (FRT) microbiome plays a vital role in maintaining vaginal health. Viruses are key regulators of other microbial ecosystems, but little is known about how the FRT viruses (virome), particularly bacteriophages that comprise the phageome, impact FRT health and dysbiosis. [...] Read more.

The female reproductive tract (FRT) microbiome plays a vital role in maintaining vaginal health. Viruses are key regulators of other microbial ecosystems, but little is known about how the FRT viruses (virome), particularly bacteriophages that comprise the phageome, impact FRT health and dysbiosis. We hypothesize that bacterial vaginosis (BV) is associated with altered FRT phageome diversity, transkingdom interplay, and bacteriophage discriminate taxa. Here, we conducted a retrospective, longitudinal analysis of vaginal swabs collected from 54 BV-positive and 46 BV-negative South African women. Bacteriome analysis revealed samples clustered into five distinct bacterial community groups (CGs), and further, bacterial alpha diversity was significantly associated with BV. Virome analysis on a subset of baseline samples showed FRT bacteriophages clustering into novel viral state types (VSTs), a viral community clustering system based on virome composition and abundance. Distinct BV bacteriophage signatures included increased alpha diversity along with discriminant Bacillus, Burkholderia, and Escherichia bacteriophages. Bacteriophage-bacteria transkingdom associations were also identified between Bacillus and Burkholderia viruses and BV-associated bacteria, providing key insights for future studies elucidating the transkingdom interactions driving BV-associated microbiome perturbations. In this cohort, bacteriophage-bacterial associations suggest complex interactions, which may play a role in the establishment and maintenance of BV. Full article

(This article belongs to the Section Bacterial Viruses)

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13 pages, 2569 KiB

Open AccessArticle

Multiple Neuraminidase Containing Influenza Virus-like Particle Vaccines Protect Mice from Avian and Human Influenza Virus Infection

by Hae-Ji Kang, Ki-Back Chu, Keon-Woong Yoon, Gi-Deok Eom, Jie Mao, Min-Ju Kim, Su-Hwa Lee, Eun-Kyung Moon and Fu-Shi Quan

Viruses 2022, 14(2), 429; https://doi.org/10.3390/v14020429 - 18 Feb 2022

Cited by 6 | Viewed by 2615

Abstract

Avian influenza virus remains a threat for humans, and vaccines preventing both avian and human influenza virus infections are needed. Since virus-like particles (VLPs) expressing single neuraminidase (NA) subtype elicited limited heterosubtypic protection, VLPs expressing multiple NA subtypes would enhance the extent of [...] Read more.

Avian influenza virus remains a threat for humans, and vaccines preventing both avian and human influenza virus infections are needed. Since virus-like particles (VLPs) expressing single neuraminidase (NA) subtype elicited limited heterosubtypic protection, VLPs expressing multiple NA subtypes would enhance the extent of heterosubtypic immunity. Here, we generated avian influenza VLP vaccines displaying H5 hemagglutinin (HA) antigen with or without avian NA subtypes (N1, N6, N8) in different combinations. BALB/c mice were intramuscularly immunized with the VLPs to evaluate the resulting homologous and heterosubtypic immunity upon challenge infections with the avian and human influenza viruses (A/H5N1, A/H3N2, A/H1N1). VLPs expressing H5 alone conferred homologous protection but not heterosubtypic protection, whereas VLPs co-expressing H5 and NA subtypes elicited both homologous and heterosubtypic protection against human influenza viruses in mice. We observed that VLP induced neuraminidase inhibitory activities (NAI), virus-neutralizing activity, and virus-specific antibody (IgG, IgA) responses were strongly correlated with the number of different NA subtype expressions on the VLPs. VLPs expressing all 3 NA subtypes resulted in the highest protection, indicated by the lowest lung titer, negligible body weight changes, and survival in immunized mice. These results suggest that expressing multiple neuraminidases in avian HA VLPs is a promising approach for developing a universal influenza A vaccine against avian and human influenza virus infections. Full article

(This article belongs to the Special Issue Virus-Like Particle Vaccines 2022)

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10 pages, 895 KiB

Open AccessReview

Approaches for Detection of Hepatitis B Virus Pre-S Gene Deletions and Pre-S Deleted Proteins and Their Application in Prediction of Higher Risk of Hepatocellular Carcinoma Development and Recurrence

by Yueh-Te Lin, Long-Bin Jeng, Ih-Jen Su and Chiao-Fang Teng

Viruses 2022, 14(2), 428; https://doi.org/10.3390/v14020428 - 18 Feb 2022

Cited by 5 | Viewed by 2414

Abstract

Hepatocellular carcinoma (HCC) is among the most common and lethal human cancers worldwide and is closely associated with chronic hepatitis B virus (HBV) infection. Pre-S deleted proteins are naturally occurring mutant forms of HBV large surface proteins that are expressed by HBV surface [...] Read more.

Hepatocellular carcinoma (HCC) is among the most common and lethal human cancers worldwide and is closely associated with chronic hepatitis B virus (HBV) infection. Pre-S deleted proteins are naturally occurring mutant forms of HBV large surface proteins that are expressed by HBV surface genes harboring deletion mutations over the pre-S gene segments. It has been well demonstrated that HBV pre-S deleted proteins function as important oncoproteins, which promote malignant phenotypes of hepatocytes through the activation of multiple oncogenic signaling pathways and result in HCC formation. The oncogenic signaling pathways activated by pre-S deleted proteins have been verified as potential therapeutic targets for the prevention of HCC development. Moreover, the presence of pre-S gene deletions and the expression of pre-S deleted proteins in the blood and liver tissues of HBV-infected patients have been evaluated as valuable biomarkers for predicting a higher risk of HCC development and recurrence after curative surgical resection. Therefore, the precise detection of pre-S gene deletions and pre-S deleted proteins holds great promise as regards identifying the patients at higher risk of HCC development and recurrence, thus aiding in more timely and better treatments to improve their survival. This review summarizes the major approaches used for the detection of pre-S gene deletions and pre-S deleted proteins, including the approaches based on Sanger DNA sequencing, pre-S gene chips, next-generation sequencing and immunohistochemistry staining, and it highlights their important applications in the prediction of higher risks of HCC development and recurrence. Full article

(This article belongs to the Special Issue State-of-the-Art Chronic Hepatitis Viruses Research in Asia)

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7 pages, 1344 KiB

Open AccessCommunication

Prevalence of MCPyV, HPyV6, HPyV7 and TSPyV in Actinic Keratosis Biopsy Specimens

by Carla Prezioso, Gabriele Brazzini, Sara Passerini, Carlotta Di Fabio, Terenzio Cosio, Sergio Bernardini, Elena Campione, Ugo Moens, Valeria Pietropaolo and Marco Ciotti

Viruses 2022, 14(2), 427; https://doi.org/10.3390/v14020427 - 18 Feb 2022

Cited by 1 | Viewed by 1530

Abstract

To date, 14 human polyomaviruses (HPyVs) have been identified using high-throughput technologies. Among them, MCPyV, HPyV6, HPyV7 and TSPyV present a skin tropism, but a causal role in skin diseases has been established only for MCPyV as a causative agent of Merkel cell [...] Read more.

To date, 14 human polyomaviruses (HPyVs) have been identified using high-throughput technologies. Among them, MCPyV, HPyV6, HPyV7 and TSPyV present a skin tropism, but a causal role in skin diseases has been established only for MCPyV as a causative agent of Merkel cell carcinoma (MCC) and TSPyV as an etiological agent of Trichodysplasia Spinulosa (TS). In the search for a possible role for cutaneous HPyVs in the development of skin malignant lesions, we investigated the prevalence of MCPyV, HPyV6, HPyV7 and TSPyV in actinic keratosis (AK), a premalignant skin lesion that has the potential to progress towards a squamous cell carcinoma (SCC). One skin lesion and one non-lesion skin from nine affected individuals were analyzed by qualitative PCR. MCPyV was detected in 9 out of 9 lesion biopsies and 6 out of 8 non-lesion biopsies. HPyV6 was detected only in healthy skin, while HPyV7 and TSPyV were not detected in any skin sample. These findings argue against a possible role of cutaneous HPyVs in AK. However, considering the small sample size analyzed, a definitive conclusion cannot be drawn. Longitudinal studies on large cohorts are warranted. Full article

(This article belongs to the Special Issue Human Polyomaviruses (HPyVs) in Human Diseases and Cancer Development)

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26 pages, 2047 KiB

Open AccessReview

Polysaccharides and Their Derivatives as Potential Antiviral Molecules

by Hadrien Claus-Desbonnet, Elsa Nikly, Vanya Nalbantova, Diana Karcheva-Bahchevanska, Stanislava Ivanova, Guillaume Pierre, Niko Benbassat, Plamen Katsarov, Philippe Michaud, Paolina Lukova and Cédric Delattre

Viruses 2022, 14(2), 426; https://doi.org/10.3390/v14020426 - 18 Feb 2022

Cited by 27 | Viewed by 4679

Abstract

In the current context of the COVID-19 pandemic, it appears that our scientific resources and the medical community are not sufficiently developed to combat rapid viral spread all over the world. A number of viruses causing epidemics have already disseminated across the world [...] Read more.

In the current context of the COVID-19 pandemic, it appears that our scientific resources and the medical community are not sufficiently developed to combat rapid viral spread all over the world. A number of viruses causing epidemics have already disseminated across the world in the last few years, such as the dengue or chinkungunya virus, the Ebola virus, and other coronavirus families such as Middle East respiratory syndrome (MERS-CoV) and severe acute respiratory syndrome (SARS-CoV). The outbreaks of these infectious diseases have demonstrated the difficulty of treating an epidemic before the creation of vaccine. Different antiviral drugs already exist. However, several of them cause side effects or have lost their efficiency because of virus mutations. It is essential to develop new antiviral strategies, but ones that rely on more natural compounds to decrease the secondary effects. Polysaccharides, which have come to be known in recent years for their medicinal properties, including antiviral activities, are an excellent alternative. They are essential for the metabolism of plants, microorganisms, and animals, and are directly extractible. Polysaccharides have attracted more and more attention due to their therapeutic properties, low toxicity, and availability, and seem to be attractive candidates as antiviral drugs of tomorrow. Full article

(This article belongs to the Special Issue De Novo Drug Design for Emerging and Reemerging Viruses)

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23 pages, 3070 KiB

Open AccessArticle

Defining the Recipe for an Optimal Rotavirus Vaccine Introduction in a High-Income Country in Europe

by Baudouin Standaert and Bernd Benninghoff

Viruses 2022, 14(2), 425; https://doi.org/10.3390/v14020425 - 18 Feb 2022

Cited by 2 | Viewed by 1548

Abstract

Observational data over 15 years of rotavirus vaccine introduction in Belgium have indicated that rotavirus hospitalisations in children aged <5 years plateaued at a higher level than expected, and was followed by biennial disease peaks. The research objective was to identify factors influencing [...] Read more.

Observational data over 15 years of rotavirus vaccine introduction in Belgium have indicated that rotavirus hospitalisations in children aged <5 years plateaued at a higher level than expected, and was followed by biennial disease peaks. The research objective was to identify factors influencing these real-world vaccine impact data. We constructed mathematical models simulating rotavirus-related hospitalisations by age group and year for those children. Two periods were defined using different model constructs. First, the vaccine uptake period encompassed the years required to cover the whole at-risk population. Second, the post-uptake period covered the years in which a new infection/disease equilibrium was reached. The models were fitted to the observational data using optimisation programmes with regression and differential equations. Modifying parameter values identified factors affecting the pattern of hospitalisations. Results indicated that starting vaccination well before the peak disease season in the first year and rapidly achieving high coverage was critical in maximising early herd effect and minimising secondary sources of infection. This, in turn, would maximise the reduction in hospitalisations and minimise the size and frequency of subsequent disease peaks. The analysis and results identified key elements to consider for countries initiating an optimal rotavirus vaccine launch programme. Full article

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

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22 pages, 32933 KiB

Open AccessArticle

PRRSV Non-Structural Proteins Orchestrate Porcine E3 Ubiquitin Ligase RNF122 to Promote PRRSV Proliferation

by Ruiqi Sun, Yanyu Guo, Xiaoyang Li, Ruiqiao Li, Jingxuan Shi, Zheng Tan, Lilin Zhang, Lei Zhang, Jun Han and Jinhai Huang

Viruses 2022, 14(2), 424; https://doi.org/10.3390/v14020424 - 18 Feb 2022

Cited by 8 | Viewed by 2312

Abstract

Ubiquitination plays a major role in immune regulation after viral infection. An alternatively spliced porcine E3 ubiquitin ligase RNF122 promoted PRRSV infection and upregulated in PRRSV-infected PAM cells was identified. We characterized the core promoter of RNF122, located between −550 to −470 bp [...] Read more.

Ubiquitination plays a major role in immune regulation after viral infection. An alternatively spliced porcine E3 ubiquitin ligase RNF122 promoted PRRSV infection and upregulated in PRRSV-infected PAM cells was identified. We characterized the core promoter of RNF122, located between −550 to −470 bp upstream of the transcription start site (TSS), which displayed significant differential transcriptional activities in regulating the transcription and expression of RNF122. The transcription factor HLTF was inhibited by nsp1α and nsp7 of PRRSV, and the transcription factor E2F complex regulated by nsp9. Together, they modulated the transcription and expression of RNF122. RNF122 could mediate K63-linked ubiquitination to raise stability of PRRSV nsp4 protein and thus promote virus replication. Moreover, RNF122 also performed K27-linked and K48-linked ubiquitination of MDA5 to degrade MDA5 and inhibit IFN production, ultimately promoted virus proliferation. In this study, we illustrate a new immune escape mechanism of PRRSV that enhances self-stability and function of viral nsp4, thus, regulating RNF122 expression to antagonize IFNα/β production. The present study broadens our knowledge of PRRSV-coding protein modulating transcription, expression and modification of host protein to counteract innate immune signaling, and may provide novel insights for the development of antiviral drugs. Full article

(This article belongs to the Section Animal Viruses)

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12 pages, 1103 KiB

Open AccessArticle

Characterization of Influenza D Virus in Danish Calves

by Nicole B. Goecke, Yuan Liang, Nina D. Otten, Charlotte K. Hjulsager and Lars E. Larsen

Viruses 2022, 14(2), 423; https://doi.org/10.3390/v14020423 - 18 Feb 2022

Cited by 5 | Viewed by 2532

Abstract

Influenza D virus (IDV) was first described in 2011 and has been found to mainly circulate among cattle and swine populations worldwide. Nasal swab samples were collected from 100 Danish calf herds (83 dairy and 17 veal herds) from 2018–2020. Influenza D virus [...] Read more.

Influenza D virus (IDV) was first described in 2011 and has been found to mainly circulate among cattle and swine populations worldwide. Nasal swab samples were collected from 100 Danish calf herds (83 dairy and 17 veal herds) from 2018–2020. Influenza D virus was detected in 12 of the herds. Samples with the lowest cycle quantification value were selected for full genome sequencing. A hemagglutinin-esterase fusion (HEF) gene sequence from a Danish IDV collected in 2015 was also included in this study. Phylogenetic analysis showed that viruses from seven of the IDV-positive herds belonged to the D/OK lineage and clustered together in the HEF tree with the IDV collected in 2015. Viruses from the four other herds belonged to the D/660 lineage, where three of the viruses clustered closely together, while the fourth virus was more phylogenetically distant in all gene segments. The high level of genetic similarity between viruses from two different herds involved in calf trading suggests that transmission occurred through the movement of calves. This study is, to our knowledge, the first to describe the characterization of IDV in calves in Denmark. Full article

(This article belongs to the Special Issue Non-A Influenza 2.0)

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13 pages, 2308 KiB

Open AccessArticle

Targeting Host PIM Protein Kinases Reduces Mayaro Virus Replication

by Madelaine Sugasti-Salazar, Dalkiria Campos, Patricia Valdés-Torres, Paola Elaine Galán-Jurado and José González-Santamaría

Viruses 2022, 14(2), 422; https://doi.org/10.3390/v14020422 - 18 Feb 2022

Cited by 2 | Viewed by 2182

Abstract

Mayaro virus (MAYV) manipulates cell machinery to successfully replicate. Thus, identifying host proteins implicated in MAYV replication represents an opportunity to discover potential antiviral targets. PIM kinases are enzymes that regulate essential cell functions and also appear to be critical factors in the [...] Read more.

Mayaro virus (MAYV) manipulates cell machinery to successfully replicate. Thus, identifying host proteins implicated in MAYV replication represents an opportunity to discover potential antiviral targets. PIM kinases are enzymes that regulate essential cell functions and also appear to be critical factors in the replication of certain viruses. In this study we explored the consequences of PIM kinase inhibition in the replication of MAYV and other arboviruses. Cytopathic effects or viral titers in samples from MAYV-, Chikungunya-, Una- or Zika-infected cells treated with PIM kinase inhibitors were evaluated using an inverted microscope or plaque-forming assays. The expression of viral proteins E1 and nsP1 in MAYV-infected cells was assessed using an immunofluorescence confocal microscope or Western blot. Our results revealed that PIM kinase inhibition partially prevented MAYV-induced cell damage and also promoted a decrease in viral titers for MAYV, UNAV and ZIKV. The inhibitory effect of PIM kinase blocking was observed for each of the MAYV strains tested and also occurred as late as 8 h post infection (hpi). Finally, PIM kinase inhibition suppressed the expression of MAYV E1 and nsP1 proteins. Taken together, these findings suggest that PIM kinases could represent an antiviral target for MAYV and other arboviruses. Full article

(This article belongs to the Section Animal Viruses)

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10 pages, 6947 KiB

Open AccessArticle

SARS-CoV-2 Delta Variant (AY.3) in the Feces of a Domestic Cat

by Olivia C. Lenz, Andrew D. Marques, Brendan J. Kelly, Kyle G. Rodino, Stephen D. Cole, Ranawaka A. P. M. Perera, Susan R. Weiss, Frederic D. Bushman and Elizabeth M. Lennon

Viruses 2022, 14(2), 421; https://doi.org/10.3390/v14020421 - 17 Feb 2022

Cited by 17 | Viewed by 7125

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have spilled over from humans to companion and wild animals since the inception of the global COVID-19 pandemic. However, whole genome sequencing data of the viral genomes that infect non-human animal species have been scant. [...] Read more.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have spilled over from humans to companion and wild animals since the inception of the global COVID-19 pandemic. However, whole genome sequencing data of the viral genomes that infect non-human animal species have been scant. Here, we detected and sequenced a SARS-CoV-2 delta variant (AY.3) in fecal samples from an 11-year-old domestic house cat previously exposed to an owner who tested positive for SARS-CoV-2. Molecular testing of two fecal samples collected 7 days apart yielded relatively high levels of viral RNA. Sequencing of the feline-derived viral genomes showed the two to be identical, and differing by between 4 and 14 single nucleotide polymorphisms in pairwise comparisons to human-derived lineage AY.3 sequences collected in the same geographic area and time period. However, several mutations unique to the feline samples reveal their divergence from this cohort on phylogenetic analysis. These results demonstrate continued spillover infections of emerging SARS-CoV-2 variants that threaten human and animal health, as well as highlight the importance of collecting fecal samples when testing for SARS-CoV-2 in animals. To the authors’ knowledge, this is the first published case of a SARS-CoV-2 delta variant in a domestic cat in the United States. Full article

(This article belongs to the Section SARS-CoV-2 and COVID-19)

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16 pages, 2779 KiB

Open AccessArticle

A Conserved Receptor-Binding Domain in the VP1u of Primate Erythroparvoviruses Determines the Marked Tropism for Erythroid Cells

by Cornelia Bircher, Jan Bieri, Ruben Assaraf, Remo Leisi and Carlos Ros

Viruses 2022, 14(2), 420; https://doi.org/10.3390/v14020420 - 17 Feb 2022

Cited by 1 | Viewed by 2216

Abstract

Parvovirus B19 (B19V) is a human pathogen with a marked tropism for erythroid progenitor cells (EPCs). The N-terminal of the VP1 unique region (VP1u) contains a receptor-binding domain (RBD), which mediates virus uptake through interaction with an as-yet-unknown receptor (VP1uR). Considering the central [...] Read more.

Parvovirus B19 (B19V) is a human pathogen with a marked tropism for erythroid progenitor cells (EPCs). The N-terminal of the VP1 unique region (VP1u) contains a receptor-binding domain (RBD), which mediates virus uptake through interaction with an as-yet-unknown receptor (VP1uR). Considering the central role of VP1uR in the virus tropism, we sought to investigate its expression profile in multiple cell types. To this end, we established a PP7 bacteriophage-VP1u bioconjugate, sharing the size and VP1u composition of native B19V capsids. The suitability of the PP7-VP1u construct as a specific and sensitive VP1uR expression marker was validated in competition assays with B19V and recombinant VP1u. VP1uR expression was exclusively detected in erythroid cells and cells reprogrammed towards the erythroid lineage. Sequence alignment and in silico protein structure prediction of the N-terminal of VP1u (N-VP1u) from B19V and other primate erythroparvoviruses (simian, rhesus, and pig-tailed) revealed a similar structure characterized by a fold of three or four α-helices. Functional studies with simian parvovirus confirmed the presence of a conserved RBD in the N-VP1u, mediating virus internalization into human erythroid cells. In summary, this study confirms the exclusive association of VP1uR expression with cells of the erythroid lineage. The presence of an analogous RBD in the VP1u from non-human primate erythroparvoviruses emphasizes their parallel evolutionary trait and zoonotic potential. Full article

(This article belongs to the Special Issue Advances in Parvovirus Research 2022)

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25 pages, 3892 KiB

Open AccessReview

How RSV Proteins Join Forces to Overcome the Host Innate Immune Response

by Tessa Van Royen, Iebe Rossey, Koen Sedeyn, Bert Schepens and Xavier Saelens

Viruses 2022, 14(2), 419; https://doi.org/10.3390/v14020419 - 17 Feb 2022

Cited by 13 | Viewed by 4364

Abstract

Respiratory syncytial virus (RSV) is the leading cause of severe acute lower respiratory tract infections in infants worldwide. Although several pattern recognition receptors (PRRs) can sense RSV-derived pathogen-associated molecular patterns (PAMPs), infection with RSV is typically associated with low to undetectable levels of [...] Read more.

Respiratory syncytial virus (RSV) is the leading cause of severe acute lower respiratory tract infections in infants worldwide. Although several pattern recognition receptors (PRRs) can sense RSV-derived pathogen-associated molecular patterns (PAMPs), infection with RSV is typically associated with low to undetectable levels of type I interferons (IFNs). Multiple RSV proteins can hinder the host’s innate immune response. The main players are NS1 and NS2 which suppress type I IFN production and signalling in multiple ways. The recruitment of innate immune cells and the production of several cytokines are reduced by RSV G. Next, RSV N can sequester immunostimulatory proteins to inclusion bodies (IBs). N might also facilitate the assembly of a multiprotein complex that is responsible for the negative regulation of innate immune pathways. Furthermore, RSV M modulates the host’s innate immune response. The nuclear accumulation of RSV M has been linked to an impaired host gene transcription, in particular for nuclear-encoded mitochondrial proteins. In addition, RSV M might also directly target mitochondrial proteins which results in a reduced mitochondrion-mediated innate immune recognition of RSV. Lastly, RSV SH might prolong the viral replication in infected cells and influence cytokine production. Full article

(This article belongs to the Special Issue Viral Strategies of Immune Evasion)

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22 pages, 1416 KiB

Open AccessReview

Structural Bases of Zoonotic and Zooanthroponotic Transmission of SARS-CoV-2

by Emily Clayton, Jacob Ackerley, Marianne Aelmans, Noor Ali, Zoe Ashcroft, Clara Ashton, Robert Barker, Vakare Budryte, Callum Burrows, Shanshan Cai, Alex Callaghan, Jake Carberry, Rebecca Chatwin, Isabella Davies, Chloe Farlow, Samuel Gamblin, Aida Iacobut, Adam Lambe, Francesca Lynch, Diana Mihalache, Amani Mokbel, Santosh Potamsetty, Zara Qadir, Jack Soden, Xiaohan Sun, Alexandru Vasile, Otto Wheeler, Mohammed A. Rohaim and Muhammad Munir Show full author list Hide full author list

Viruses 2022, 14(2), 418; https://doi.org/10.3390/v14020418 - 17 Feb 2022

Cited by 8 | Viewed by 3873

Abstract

The emergence of multiple variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the importance of possible animal-to-human (zoonotic) and human-to-animal (zooanthroponotic) transmission and potential spread within animal species. A range of animal species have been verified for SARS-CoV-2 susceptibility, either in [...] Read more.

The emergence of multiple variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the importance of possible animal-to-human (zoonotic) and human-to-animal (zooanthroponotic) transmission and potential spread within animal species. A range of animal species have been verified for SARS-CoV-2 susceptibility, either in vitro or in vivo. However, the molecular bases of such a broad host spectrum for the SARS-CoV-2 remains elusive. Here, we structurally and genetically analysed the interaction between the spike protein, with a particular focus on receptor binding domains (RBDs), of SARS-CoV-2 and its receptor angiotensin-converting enzyme 2 (ACE2) for all conceivably susceptible groups of animals to gauge the structural bases of the SARS-CoV-2 host spectrum. We describe our findings in the context of existing animal infection-based models to provide a foundation on the possible virus persistence in animals and their implications in the future eradication of COVID-19. Full article

(This article belongs to the Special Issue Emerging Zoonotic Viral Diseases)

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13 pages, 2578 KiB

Open AccessReview

Current Status of Genetically Modified Pigs That Are Resistant to Virus Infection

by Hongming Yuan, Lin Yang, Yuanzhu Zhang, Wenyu Xiao, Ziru Wang, Xiaochun Tang, Hongsheng Ouyang and Daxin Pang

Viruses 2022, 14(2), 417; https://doi.org/10.3390/v14020417 - 17 Feb 2022

Cited by 5 | Viewed by 4302

Abstract

Pigs play an important role in agriculture and biomedicine. The globally developing swine industry must address the challenges presented by swine-origin viruses, including ASFV (African swine fever virus), PRRSV (porcine reproductive and respiratory syndrome virus), PEDV (porcine epidemic diarrhea virus), PRV (pseudorabies virus), [...] Read more.

Pigs play an important role in agriculture and biomedicine. The globally developing swine industry must address the challenges presented by swine-origin viruses, including ASFV (African swine fever virus), PRRSV (porcine reproductive and respiratory syndrome virus), PEDV (porcine epidemic diarrhea virus), PRV (pseudorabies virus), CSFV (classical swine fever virus), TGEV (transmissible gastroenteritis virus), et al. Despite sustained efforts by many government authorities, these viruses are still widespread. Currently, gene-editing technology has been successfully used to generate antiviral pigs, which offers the possibility for increasing animal disease tolerance and improving animal economic traits in the future. Here, we summarized the current advance in knowledge regarding the host factors in virus infection and the current status of genetically modified pigs that are resistant to virus infection in the world. There has not been any report on PEDV-resistant pigs, ASFV-resistant pigs, and PRV-resistant pigs owing to the poor understanding of the key host factors in virus infection. Furthermore, we summarized the remaining problems in producing virus-resistant pigs, and proposed several potential methods to solve them. Using genome-wide CRISPR/Cas9 library screening to explore the key host receptors in virus infection may be a feasible method. At the same time, exploring the key amino acids of host factors in virus infection with library screening based on ABEs and CBEs (Bes) may provide creative insight into producing antiviral pigs in the future. Full article

(This article belongs to the Special Issue State-of-the-Art Porcine Virus Research in China)

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