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Viruses, Volume 15, Issue 5 (May 2023) – 188 articles

Cover Story (view full-size image): Respiratory syncytial virus (RSV) is an important cause of acute respiratory disease, which is partly mediated through a conserved chemokine mimic, i.e., a CX3C motif on the attachment (G) protein. In this Special Issue, Bergeron et. al. describes two anti-RSV G mAbs (3D3 and 2D10) that bind distinct conformational epitopes on the RSV G protein central conserved domain. The findings show that antibodies binding to the RSV G protein at or near the CX3C motif reduce immune pathology and provide protection against disease. These mAbs neutralize RSV and improve immune correlates of disease protection in a prophylactic and therapeutic regimen in a mouse model. View this paper
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20 pages, 1287 KiB  
Review
Viral Co-Infections and Antiviral Immunity in Honey Bees
by Tristan Durand, Anne Bonjour-Dalmon and Eric Dubois
Viruses 2023, 15(5), 1217; https://doi.org/10.3390/v15051217 - 22 May 2023
Cited by 1 | Viewed by 2230
Abstract
Over the past few decades, honey bees have been facing an increasing number of stressors. Beyond individual stress factors, the synergies between them have been identified as a key factor in the observed increase in colony mortality. However, these interactions are numerous and [...] Read more.
Over the past few decades, honey bees have been facing an increasing number of stressors. Beyond individual stress factors, the synergies between them have been identified as a key factor in the observed increase in colony mortality. However, these interactions are numerous and complex and call for further research. Here, in line with our need for a systemic understanding of the threats that they pose to bee health, we review the interactions between honey bee viruses. As viruses are obligate parasites, the interactions between them not only depend on the viruses themselves but also on the immune responses of honey bees. Thus, we first summarise our current knowledge of the antiviral immunity of honey bees. We then review the interactions between specific pathogenic viruses and their interactions with their host. Finally, we draw hypotheses from the current literature and suggest directions for future research. Full article
(This article belongs to the Special Issue Molecular Virus-Insect Interactions)
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13 pages, 2667 KiB  
Article
Identification of Host Proteins Interacting with IBV S1 Based on Tracheal Organ Culture
by Huandong Zhang, Houli Cai, Qingyang Li, Chengxiu Fang, Li Peng, Jianing Lan, Jiyong Zhou and Min Liao
Viruses 2023, 15(5), 1216; https://doi.org/10.3390/v15051216 - 22 May 2023
Cited by 4 | Viewed by 1242
Abstract
Infectious bronchitis virus (IBV) belongs to the gamma-coronavirus genus of Coronaviridae and causes serious infectious diseases in the poultry industry. However, only a few IBV strains can infect avian passage cell lines, seriously hindering the progress of basic research on IBV pathogenesis. Whereas [...] Read more.
Infectious bronchitis virus (IBV) belongs to the gamma-coronavirus genus of Coronaviridae and causes serious infectious diseases in the poultry industry. However, only a few IBV strains can infect avian passage cell lines, seriously hindering the progress of basic research on IBV pathogenesis. Whereas IBV field strains can replicate in tracheal ring organ culture (TOC) without any previous adaptation in chicken embryos or primary cells. In this study, to investigate the potential use of TOC as an in vitro infection model for the study of IBV-host interaction, we first established a chicken embryo TOC culture system and carried out an investigation on the IBV replication kinetics in the system. We found that the selected strains of the IBV GI-1, GI-7, GI-13, GI-19, and GI-22 genotypes could successfully replicate in TOC and bring about damage to the infected trachea. Next, we identified host proteins of the chicken embryo trachea that interact with the IBV S1 protein by immunoprecipitation and protein mass spectrometry. A total of 127 candidate proteins were initially identified with major involvement in cell adhesion pathways and apoptosis- and autophagy-related pathways. The heat shock protein 70 (HSP70) was selected for further investigation in the interaction with IBV viral proteins. Our results showed that HSP70 interacted with IBV S1 in both TOC and CEK cells, whereas HSP70 overexpression inhibited viral replication. This study indicates that TOC is a good system for the elucidation of IBV-host interactions and HSP70 is a potential host antiviral factor. Full article
(This article belongs to the Special Issue Infectious Bronchitis Virus)
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21 pages, 419 KiB  
Review
Autoantibodies to Interferons in Infectious Diseases
by Eugenia Quiros-Roldan, Alessandra Sottini, Simona Giulia Signorini, Federico Serana, Giorgio Tiecco and Luisa Imberti
Viruses 2023, 15(5), 1215; https://doi.org/10.3390/v15051215 - 22 May 2023
Cited by 8 | Viewed by 2193
Abstract
Anti-cytokine autoantibodies and, in particular, anti-type I interferons are increasingly described in association with immunodeficient, autoimmune, and immune-dysregulated conditions. Their presence in otherwise healthy individuals may result in a phenotype characterized by a predisposition to infections with several agents. For instance, anti-type I [...] Read more.
Anti-cytokine autoantibodies and, in particular, anti-type I interferons are increasingly described in association with immunodeficient, autoimmune, and immune-dysregulated conditions. Their presence in otherwise healthy individuals may result in a phenotype characterized by a predisposition to infections with several agents. For instance, anti-type I interferon autoantibodies are implicated in Coronavirus Disease 19 (COVID-19) pathogenesis and found preferentially in patients with critical disease. However, autoantibodies were also described in the serum of patients with viral, bacterial, and fungal infections not associated with COVID-19. In this review, we provide an overview of anti-cytokine autoantibodies identified to date and their clinical associations; we also discuss whether they can act as enemies or friends, i.e., are capable of acting in a beneficial or harmful way, and if they may be linked to gender or immunosenescence. Understanding the mechanisms underlying the production of autoantibodies could improve the approach to treating some infections, focusing not only on pathogens, but also on the possibility of a low degree of autoimmunity in patients. Full article
(This article belongs to the Special Issue Innate Immunity to Virus Infection 2023)
2 pages, 175 KiB  
Editorial
Concluding Remarks for the Special Issue on RNA Viruses and Antibody Response
by Yiu-Wing KAM
Viruses 2023, 15(5), 1214; https://doi.org/10.3390/v15051214 - 22 May 2023
Viewed by 1000
Abstract
Infectious diseases represent one of the major public health concerns on the global level [...] Full article
(This article belongs to the Special Issue RNA Viruses and Antibody Response)
13 pages, 1612 KiB  
Conference Report
Foundation of the Belgian Society for Viruses of Microbes and Meeting Report of Its Inaugural Symposium
by Agnieszka Latka, Abram Aertsen, Dimitri Boeckaerts, Bob Blasdel, Pieter-Jan Ceyssens, Abel Garcia-Pino, Annika Gillis, Rob Lavigne, Gipsi Lima-Mendez, Jelle Matthijnssens, Jolien Onsea, Eveline Peeters, Jean-Paul Pirnay, Damien Thiry, Dieter Vandenheuvel, Els Van Mechelen, Jolien Venneman, Gilbert Verbeken, Jeroen Wagemans and Yves Briers
Viruses 2023, 15(5), 1213; https://doi.org/10.3390/v15051213 - 22 May 2023
Viewed by 1648
Abstract
The Belgian Society for Viruses of Microbes (BSVoM) was founded on 9 June 2022 to capture and enhance the collaborative spirit among the expanding community of microbial virus researchers in Belgium. The sixteen founders are affiliated to fourteen different research entities across academia, [...] Read more.
The Belgian Society for Viruses of Microbes (BSVoM) was founded on 9 June 2022 to capture and enhance the collaborative spirit among the expanding community of microbial virus researchers in Belgium. The sixteen founders are affiliated to fourteen different research entities across academia, industry and government. Its inaugural symposium was held on 23 September 2022 in the Thermotechnical Institute at KU Leuven. The meeting program covered three thematic sessions launched by international keynote speakers: (1) virus–host interactions, (2) viral ecology, evolution and diversity and (3) present and future applications. During the one-day symposium, four invited keynote lectures, ten selected talks and eight student pitches were given along with 41 presented posters. The meeting hosted 155 participants from twelve countries. Full article
(This article belongs to the Special Issue Research on Viruses of Microbes in Belgium)
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11 pages, 815 KiB  
Article
The Impact of the Definitions of Clinical Phases on the Profiles of Grey-Zone Patients with Chronic Hepatitis B Virus Infection
by Xiaoqian Xu, Hao Wang, Shan Shan, Yameng Sun, Xiaoyuan Xu, Hong You, Jidong Jia, Hui Zhuang, Yuanyuan Kong and on behalf of the China Registry of Hepatitis B (CR-HepB) Group
Viruses 2023, 15(5), 1212; https://doi.org/10.3390/v15051212 - 22 May 2023
Cited by 2 | Viewed by 1553
Abstract
We aim to investigate the impact of different clinical phases’ definitions of chronic hepatitis B (CHB) infection on the profiles of grey zone, based on HBV guidelines set by the Chinese Society of Hepatology and Chinese Society of Infectious Diseases (CSH/CSID, 2022 version) [...] Read more.
We aim to investigate the impact of different clinical phases’ definitions of chronic hepatitis B (CHB) infection on the profiles of grey zone, based on HBV guidelines set by the Chinese Society of Hepatology and Chinese Society of Infectious Diseases (CSH/CSID, 2022 version) and guidelines set by the American Association for the Study of Liver Diseases (AASLD, 2018 version). We retrospectively examined untreated CHB patients enrolled in the China Registry of Hepatitis B database. Patients’ clinical phases were determined as per CSH/CSID and AASLD. Liver fibrosis was estimated by FIB-4 and/or APRI. Among 3462 CHB patients, 56.9% and 41.7% fell into the grey zone based on AASLD and CSH/CSID. Compared with grey zone patients as per AASLD, those under CSH/CSID guidelines showed lower levels of median ALT (26.0 vs. 37.0 U/L, p < 0.001), AST (25.0 vs. 29.4 U/L, p < 0.001) and APRI (0.3 vs. 0.4, p < 0.001), and lower rates of advanced fibrosis estimated by APRI (7.9% vs. 11.4% p = 0.001), but comparable rates by FIB-4 (13.0% vs. 14.1%, p = 0.389). With the stepwise lowering of ALT upper limits of normal (ULN) values from 50/40 U/L for males/females to 40/40 U/L, 35/25 U/L and 30/19 U/L, the proportions of grey zone patients as per CSH/CSID declined from 46.7% to 41.7%, 34.3% and 28.8%, respectively, whereas they remained stable (55.7%, 56.2%, 56.9% and 57.0%) as per AASLD. Compared with the AASLD guidelines, CSH/CSID guidelines leave fewer and less severe patients in the grey zone. Lowering ALT ULN values reduces the number of grey zone patients as per CSH/CSID, but not under AASLD guidelines. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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32 pages, 1388 KiB  
Review
Natural Products and Derivatives as Potential Zika virus Inhibitors: A Comprehensive Review
by Rosângela Santos Pereira, Françoise Camila Pereira Santos, Priscilla Rodrigues Valadares Campana, Vivian Vasconcelos Costa, Rodrigo Maia de Pádua, Daniele G. Souza, Mauro Martins Teixeira and Fernão Castro Braga
Viruses 2023, 15(5), 1211; https://doi.org/10.3390/v15051211 - 20 May 2023
Cited by 7 | Viewed by 2281
Abstract
Zika virus (ZIKV) is an arbovirus whose infection in humans can lead to severe outcomes. This article reviews studies reporting the anti-ZIKV activity of natural products (NPs) and derivatives published from 1997 to 2022, which were carried out with NPs obtained from plants [...] Read more.
Zika virus (ZIKV) is an arbovirus whose infection in humans can lead to severe outcomes. This article reviews studies reporting the anti-ZIKV activity of natural products (NPs) and derivatives published from 1997 to 2022, which were carried out with NPs obtained from plants (82.4%) or semisynthetic/synthetic derivatives, fungi (3.1%), bacteria (7.6%), animals (1.2%) and marine organisms (1.9%) along with miscellaneous compounds (3.8%). Classes of NPs reported to present anti-ZIKV activity include polyphenols, triterpenes, alkaloids, and steroids, among others. The highest values of the selectivity index, the ratio between cytotoxicity and antiviral activity (SI = CC50/EC50), were reported for epigallocatechin gallate (SI ≥ 25,000) and anisomycin (SI ≥ 11,900) obtained from Streptomyces bacteria, dolastane (SI = 1246) isolated from the marine seaweed Canistrocarpus cervicorni, and the flavonol myricetin (SI ≥ 862). NPs mostly act at the stages of viral adsorption and internalization in addition to presenting virucidal effect. The data demonstrate the potential of NPs for developing new anti-ZIKV agents and highlight the lack of studies addressing their molecular mechanisms of action and pre-clinical studies of efficacy and safety in animal models. To the best of our knowledge, none of the active compounds has been submitted to clinical studies. Full article
(This article belongs to the Special Issue Recent Advances in Antiviral Natural Products)
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15 pages, 3586 KiB  
Article
Successful Bacteriophage-Antibiotic Combination Therapy against Multidrug-Resistant Pseudomonas aeruginosa Left Ventricular Assist Device Driveline Infection
by Karlis Racenis, Janis Lacis, Dace Rezevska, Laima Mukane, Aija Vilde, Ints Putnins, Sarah Djebara, Maya Merabishvili, Jean-Paul Pirnay, Marika Kalnina, Aivars Petersons, Peteris Stradins, Sandis Maurins and Juta Kroica
Viruses 2023, 15(5), 1210; https://doi.org/10.3390/v15051210 - 20 May 2023
Cited by 5 | Viewed by 1986
Abstract
There is considerable interest in the use of bacteriophages (phages) to treat Pseudomonas aeruginosa infections associated with left ventricular assist devices (LVADs). These infections are often challenging to manage due to high rates of multidrug resistance and biofilm formation, which could potentially be [...] Read more.
There is considerable interest in the use of bacteriophages (phages) to treat Pseudomonas aeruginosa infections associated with left ventricular assist devices (LVADs). These infections are often challenging to manage due to high rates of multidrug resistance and biofilm formation, which could potentially be overcome with the use of phages. We report a case of a 54-year-old man with relapsing multidrug-resistant P. aeruginosa LVAD driveline infection, who was treated with a combination of two lytic antipseudomonal phages administered intravenously and locally. Treatment was combined with LVAD driveline repositioning and systemic antibiotic administration, resulting in a successful outcome with clinical cure and eradication of the targeted bacteria. However, laboratory in vitro models showed that phages alone could not eradicate biofilms but could prevent biofilm formation. Phage-resistant bacterial strains evolved in biofilm models and showed decreased susceptibility to the phages used. Further studies are needed to understand the complexity of phage resistance and the interaction of phages and antibiotics. Our results indicate that the combination of phages, antibiotics, and surgical intervention can have great potential in treating LVAD-associated infections. More than 21 months post-treatment, our patient remains cured of the infection. Full article
(This article belongs to the Section Bacterial Viruses)
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19 pages, 2685 KiB  
Article
Area Wide Monitoring of Plant and Honey Bee (Apis mellifera) Viruses in Blueberry (Vaccinium corymbosum) Agroecosystems Facilitated by Honey Bee Pollination
by Eunseo Lee, Raj Vansia, James Phelan, Andrea Lofano, Adam Smith, Aiming Wang, Guillaume J. Bilodeau, Stephen F. Pernal, M. Marta Guarna, Michael Rott and Jonathan S. Griffiths
Viruses 2023, 15(5), 1209; https://doi.org/10.3390/v15051209 - 20 May 2023
Cited by 3 | Viewed by 2038
Abstract
Healthy agroecosystems are dependent on a complex web of factors and inter-species interactions. Flowers are hubs for pathogen transmission, including the horizontal or vertical transmission of plant-viruses and the horizontal transmission of bee-viruses. Pollination by the European honey bee (Apis mellifera) [...] Read more.
Healthy agroecosystems are dependent on a complex web of factors and inter-species interactions. Flowers are hubs for pathogen transmission, including the horizontal or vertical transmission of plant-viruses and the horizontal transmission of bee-viruses. Pollination by the European honey bee (Apis mellifera) is critical for industrial fruit production, but bees can also vector viruses and other pathogens between individuals. Here, we utilized commercial honey bee pollination services in blueberry (Vaccinium corymbosum) farms for a metagenomics-based bee and plant virus monitoring system. Following RNA sequencing, viruses were identified by mapping reads to a reference sequence database through the bioinformatics portal Virtool. In total, 29 unique plant viral species were found at two blueberry farms in British Columbia (BC). Nine viruses were identified at one site in Ontario (ON), five of which were not identified in BC. Ilarviruses blueberry shock virus (BlShV) and prune dwarf virus (PDV) were the most frequently detected viruses in BC but absent in ON, while nepoviruses tomato ringspot virus and tobacco ringspot virus were common in ON but absent in BC. BlShV coat protein (CP) nucleotide sequences were nearly identical in all samples, while PDV CP sequences were more diverse, suggesting multiple strains of PDV circulating at this site. Ten bee-infecting viruses were identified, with black queen cell virus frequently detected in ON and BC. Area-wide bee-mediated pathogen monitoring can provide new insights into the diversity of viruses present in, and the health of, bee-pollination ecosystems. This approach can be limited by a short sampling season, biased towards pollen-transmitted viruses, and the plant material collected by bees can be very diverse. This can obscure the origin of some viruses, but bee-mediated virus monitoring can be an effective preliminary monitoring approach. Full article
(This article belongs to the Special Issue Plant Virus Metagenomics)
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14 pages, 3306 KiB  
Article
Virulent Phage vB_EfaS_WH1 Removes Enterococcus faecalis Biofilm and Inhibits Its Growth on the Surface of Chicken Meat
by Xinxin Jin, Xiuxiu Sun, Zui Wang, Junfeng Dou, Zhengdan Lin, Qin Lu, Tengfei Zhang, Guoyuan Wen, Huabin Shao, Guofu Cheng and Qingping Luo
Viruses 2023, 15(5), 1208; https://doi.org/10.3390/v15051208 - 20 May 2023
Cited by 1 | Viewed by 1413
Abstract
Enterococcus faecalis is a potential animal and human pathogen. Improper use of antibiotics encourages resistance. Bacteriophages and their derivatives are promising for treating drug-resistant bacterial infections. In this study, phylogenetic and electron microscopy analyses of phage vB_EfaS_WH1 (WH1) isolated from chicken feces revealed [...] Read more.
Enterococcus faecalis is a potential animal and human pathogen. Improper use of antibiotics encourages resistance. Bacteriophages and their derivatives are promising for treating drug-resistant bacterial infections. In this study, phylogenetic and electron microscopy analyses of phage vB_EfaS_WH1 (WH1) isolated from chicken feces revealed it to be a novel phage in the family Siphoviridae. WH1 showed good pH stability (4–11), temperature tolerance (4–60 °C), and broad E. faecalis host range (60% of isolates). Genome sequencing revealed a 56,357 bp double-stranded DNA genome with a G+C content of 39.21%. WH1 effectively destroyed E. faecalis EF01 biofilms, even at low concentrations. When WH1 was applied at 1 × 105 to 1 × 109 PFU/g to chicken breast samples stored at 4 °C, surface growing E. faecalis were appreciably eradicated after 24 h. The phage WH1 showed good antibacterial activity, which could be used as a potential biocontrol agent to reduce the formation of E. faecalis biofilm, and could also be used as an alternative for the control of E. faecalis in chicken products. Full article
(This article belongs to the Special Issue Bacteriophages and Biofilms 2.0)
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19 pages, 2533 KiB  
Article
Porcine Circovirus Modulates Swine Influenza Virus Replication in Pig Tracheal Epithelial Cells and Porcine Alveolar Macrophages
by Yaima Burgher Pulgaron, Chantale Provost, Marie-Jeanne Pesant and Carl A. Gagnon
Viruses 2023, 15(5), 1207; https://doi.org/10.3390/v15051207 - 20 May 2023
Cited by 2 | Viewed by 1500
Abstract
The pathogenesis of porcine circovirus type 2b (PCV2b) and swine influenza A virus (SwIV) during co-infection in swine respiratory cells is poorly understood. To elucidate the impact of PCV2b/SwIV co-infection, newborn porcine tracheal epithelial cells (NPTr) and immortalized porcine alveolar macrophages (iPAM 3D4/21) [...] Read more.
The pathogenesis of porcine circovirus type 2b (PCV2b) and swine influenza A virus (SwIV) during co-infection in swine respiratory cells is poorly understood. To elucidate the impact of PCV2b/SwIV co-infection, newborn porcine tracheal epithelial cells (NPTr) and immortalized porcine alveolar macrophages (iPAM 3D4/21) were co-infected with PCV2b and SwIV (H1N1 or H3N2 genotype). Viral replication, cell viability and cytokine mRNA expression were determined and compared between single-infected and co-infected cells. Finally, 3′mRNA sequencing was performed to identify the modulation of gene expression and cellular pathways in co-infected cells. It was found that PCV2b significantly decreased or improved SwIV replication in co-infected NPTr and iPAM 3D4/21 cells, respectively, compared to single-infected cells. Interestingly, PCV2b/SwIV co-infection synergistically up-regulated IFN expression in NPTr cells, whereas in iPAM 3D4/21 cells, PCV2b impaired the SwIV IFN induced response, both correlating with SwIV replication modulation. RNA-sequencing analyses revealed that the modulation of gene expression and enriched cellular pathways during PCV2b/SwIV H1N1 co-infection is regulated in a cell-type-dependent manner. This study revealed different outcomes of PCV2b/SwIV co-infection in porcine epithelial cells and macrophages and provides new insights on porcine viral co-infections pathogenesis. Full article
(This article belongs to the Section Animal Viruses)
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10 pages, 297 KiB  
Article
Clinical and Epidemiological Characteristics of Neurocryptococcosis Associated with HIV in Northeastern Brazil
by Ertênia Paiva Oliveira, Bruna Rodrigues de Sousa, Jucieli Firmino de Freitas, Rejane Pereira Neves, Moacir Batista Jucá, Paulo Sérgio Ramos de Araújo, Jailton Lobo da Costa Lima, Maria Amélia Vieira Maciel and Reginaldo Gonçalves de Lima-Neto
Viruses 2023, 15(5), 1206; https://doi.org/10.3390/v15051206 - 20 May 2023
Cited by 1 | Viewed by 1129
Abstract
Cryptococcal meningitis is a serious infection of the central nervous system that is predominant in developing countries, caused by fungi of the genus Cryptococcus, and which affects immunosuppressed patients, especially those with HIV. Here, we aim to diagnose and characterize the clinical–epidemiological [...] Read more.
Cryptococcal meningitis is a serious infection of the central nervous system that is predominant in developing countries, caused by fungi of the genus Cryptococcus, and which affects immunosuppressed patients, especially those with HIV. Here, we aim to diagnose and characterize the clinical–epidemiological profile of cryptococcosis in patients admitted to two tertiary public hospitals in northeastern Brazil. The study is divided into three moments: (1) the isolation of fungus and diagnosis from biological samples collected between 2017 and 2019, (2) a description of the clinical and epidemiological characteristics of the patients, and (3) the experimental tests related to an in vitro susceptibility antifungal profile. The species were identified by MALDI-TOF/MS. Among the 100 patients evaluated, 24 (24.5%) were diagnosed with cryptococcosis based on positive culture. Clinical–epidemiological analysis showed a slightly higher prevalence in men between 30 and 39 years. When comparing the date of HIV diagnosis and the development of cryptococcosis, it was observed that 50% received the diagnosis of infection by cryptococcosis after or equal to a period of 12 months from being diagnosed with HIV; the other 50% received it within the first 30 days of the HIV diagnosis. Neurocryptococcosis was the most prevalent clinical form, and, at the time of hospital admission, the most common clinical signs were high fever (75%), intense headache (62.50%), and neck stiffness (33.33%). The cerebrospinal fluid showed 100% sensitivity and positivity for direct examination by India ink, and fungal culture. The mortality rate in this study was 46% (11/24), a lower rate than in the other literature. An antifungigram showed that 20 (83.33%) isolates were susceptible to amphotericin B and 15 (62.5%) to fluconazole. Mass spectrometry identified 100% of the isolates as Cryptococcus neoformans. In Brazil, this infection is not mandatory notifiable. Therefore, although there is little information on the subject, it is obsolete and does not express the reality of the facts, mainly in the northeast region, where this information is insufficient. The data obtained in this research contribute to the epidemiological knowledge of this mycosis in Brazil and will serve as a basis for future globally comparative epidemiological studies. Full article
(This article belongs to the Special Issue HIV Neurological Disorders)
11 pages, 257 KiB  
Article
Clinical Features of COVID-19 in Pediatric Rheumatic Diseases: 2020–2022 Survey of the Pediatric Rheumatology Association of Japan
by Hiroyuki Wakiguchi, Utako Kaneko, Satoshi Sato, Tomoyuki Imagawa, Hidehiko Narazaki and Takako Miyamae
Viruses 2023, 15(5), 1205; https://doi.org/10.3390/v15051205 - 20 May 2023
Cited by 2 | Viewed by 1682
Abstract
Coronavirus disease 2019 (COVID-19) in children can be compounded by concurrent diseases and immunosuppressants. For the first time, we aimed to report the clinical features of concurrent COVID-19 and pediatric rheumatic disease (PRD) in Japan. Pediatric Rheumatology Association of Japan members were surveyed [...] Read more.
Coronavirus disease 2019 (COVID-19) in children can be compounded by concurrent diseases and immunosuppressants. For the first time, we aimed to report the clinical features of concurrent COVID-19 and pediatric rheumatic disease (PRD) in Japan. Pediatric Rheumatology Association of Japan members were surveyed between 1 April 2020 and 31 August 2022. Outcome measurements included the clinical features of concurrent PRD and COVID-19. Questionnaire responses were obtained from 38 hospitals. Thirty-one hospitals (82%) had children with PRD and COVID-19. The female-to-male ratio in these children (n = 156) was 7:3, with half aged 11–15 years. The highest proportion of children with PRD and COVID-19 was accounted for by juvenile idiopathic arthritis (52%), followed by systemic lupus erythematosus (24%), juvenile dermatomyositis (5%), scleroderma (4%), and Takayasu arteritis (3%). Of children with PRD, a significant majority (97%) were found to be asymptomatic (10%) or presented with mild symptoms (87%) of the COVID-19 infection. No severe cases or deaths were observed. Regarding the use of glucocorticoids, immunosuppressants, or biologics for PRD treatment before COVID-19, no significant difference was found between asymptomatic/mild and moderate COVID-19 in children with PRD. Therefore, COVID-19 is not a threat to children with PRD in Japan. Full article
(This article belongs to the Special Issue Pediatric Respiratory Viral Infection)
10 pages, 2418 KiB  
Article
β-Glucan Induces Training Immunity to Promote Antiviral Activity by Activating TBK1
by Guolei Wang, Zhiqiang Li, Mingfu Tian, Xianghua Cui, Jun’e Ma, Siyu Liu, Chenglin Ye, Li Yuan, Muhammad Suhaib Qudus, Uzair Afaq, Kailang Wu, Xinghui Liu and Chengliang Zhu
Viruses 2023, 15(5), 1204; https://doi.org/10.3390/v15051204 - 19 May 2023
Cited by 2 | Viewed by 2178
Abstract
Many studies have shown that β-glucan induces a trained immune phenotype in innate immune cells to defend against bacterial and fungal infections. The specific mechanism involves cellular metabolism and epigenetic reprogramming. However, it is unclear whether β-glucan plays a role in antiviral infection. [...] Read more.
Many studies have shown that β-glucan induces a trained immune phenotype in innate immune cells to defend against bacterial and fungal infections. The specific mechanism involves cellular metabolism and epigenetic reprogramming. However, it is unclear whether β-glucan plays a role in antiviral infection. Therefore, this study investigated the role of trained immunity induced by Candida albicans and β-glucan in antiviral innate immunity. It showed that C. albicans and β-glucan promoted the expression of interferon-β (IFN-β) and interleukin-6 (IL-6) in mouse macrophages triggered by viral infection. In addition, β-glucan pretreatment attenuated the pathological damage induced by the virus in mouse lungs and promoted the expression of IFN-β. Mechanistically, β-glucan could promote the phosphorylation and ubiquitination of TANK Binding Kinase 1 (TBK1), a key protein of the innate immune pathway. These results suggest that β-glucan can promote innate antiviral immunity, and this bioactive material may be a potential therapeutic target for antiviral treatment. Full article
(This article belongs to the Special Issue In Memory of Jianguo Wu)
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15 pages, 4282 KiB  
Article
Poly(I:C) Induces Distinct Liver Cell Type-Specific Responses in Hepatitis B Virus-Transgenic Mice In Vitro, but Fails to Induce These Signals In Vivo
by Stefan Schefczyk, Xufeng Luo, Yaojie Liang, Martin Trippler, Mengji Lu, Heiner Wedemeyer, Hartmut H. Schmidt and Ruth Broering
Viruses 2023, 15(5), 1203; https://doi.org/10.3390/v15051203 - 19 May 2023
Cited by 1 | Viewed by 1417
Abstract
Immunopathology in hepatitis B virus (HBV) infection is driven by innate and adaptive immunity. Whether the hepatitis B surface antigen (HBsAg) affects hepatic antiviral signalling was investigated in HBV-transgenic mouse models that either accumulate (Alb/HBs, Tg[Alb1HBV]Bri44), lack (Tg1.4HBV-s-mut3) or secrete (Tg1.4HBV-s-rec (F1, Tg1.4HBV-s-mut [...] Read more.
Immunopathology in hepatitis B virus (HBV) infection is driven by innate and adaptive immunity. Whether the hepatitis B surface antigen (HBsAg) affects hepatic antiviral signalling was investigated in HBV-transgenic mouse models that either accumulate (Alb/HBs, Tg[Alb1HBV]Bri44), lack (Tg1.4HBV-s-mut3) or secrete (Tg1.4HBV-s-rec (F1, Tg1.4HBV-s-mut × Alb/HBs) the HBsAg. Herein, the responsiveness of TLR3 and RIG-I in primary parenchymal and non-parenchymal liver cells was determined in vitro and in vivo. Cell type-specific and mouse strain-dependent interferon, cytokine and chemokine expression were observed by LEGENDplex™ and validated by quantitative PCR. In vitro, the hepatocytes, liver sinusoidal endothelial cells and Kupffer cells of Tg1.4HBV-s-rec mice showed poly(I:C) susceptibilities similar to the wild-type controls, while in the remaining leucocyte fraction the interferon, cytokine and chemokine induction was reduced. On the contrary, poly(I:C)-injected 1.4TgHBV-s-rec mice showed suppressed interferon, cytokine and chemokine levels in hepatocytes but increased levels in the leucocyte fraction. Thus, we concluded that liver cells of Tg1.4HBV-s-rec mice, which produce HBV particles and release the HBsAg, responded to exogenous TLR3/RIG-I stimuli in vitro but exhibited a tolerogenic environment in vivo. Full article
(This article belongs to the Special Issue Pathophysiology of Viral Hepatitis)
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36 pages, 988 KiB  
Review
Fungal Viruses Unveiled: A Comprehensive Review of Mycoviruses
by Bianca Hough, Emma Steenkamp, Brenda Wingfield and David Read
Viruses 2023, 15(5), 1202; https://doi.org/10.3390/v15051202 - 19 May 2023
Cited by 14 | Viewed by 5700
Abstract
Mycoviruses (viruses of fungi) are ubiquitous throughout the fungal kingdom and are currently classified into 23 viral families and the genus botybirnavirus by the International Committee on the Taxonomy of Viruses (ICTV). The primary focus of mycoviral research has been on mycoviruses that [...] Read more.
Mycoviruses (viruses of fungi) are ubiquitous throughout the fungal kingdom and are currently classified into 23 viral families and the genus botybirnavirus by the International Committee on the Taxonomy of Viruses (ICTV). The primary focus of mycoviral research has been on mycoviruses that infect plant pathogenic fungi, due to the ability of some to reduce the virulence of their host and thus act as potential biocontrol against these fungi. However, mycoviruses lack extracellular transmission mechanisms and rely on intercellular transmission through the hyphal anastomosis, which impedes successful transmission between different fungal strains. This review provides a comprehensive overview of mycoviruses, including their origins, host range, taxonomic classification into families, effects on their fungal counterparts, and the techniques employed in their discovery. The application of mycoviruses as biocontrol agents of plant pathogenic fungi is also discussed. Full article
(This article belongs to the Collection Mycoviruses)
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18 pages, 597 KiB  
Article
A COVID-19 Infection Model Considering the Factors of Environmental Vectors and Re-Positives and Its Application to Data Fitting in Japan and Italy
by Shimeng Dong, Jinlong Lv, Wanbiao Ma and Boralahala Gamage Sampath Aruna Pradeep
Viruses 2023, 15(5), 1201; https://doi.org/10.3390/v15051201 - 19 May 2023
Viewed by 1059
Abstract
COVID-19, which broke out globally in 2019, is an infectious disease caused by a novel strain of coronavirus, and its spread is highly contagious and concealed. Environmental vectors play an important role in viral infection and transmission, which brings new difficulties and challenges [...] Read more.
COVID-19, which broke out globally in 2019, is an infectious disease caused by a novel strain of coronavirus, and its spread is highly contagious and concealed. Environmental vectors play an important role in viral infection and transmission, which brings new difficulties and challenges to disease prevention and control. In this paper, a type of differential equation model is constructed according to the spreading functions and characteristics of exposed individuals and environmental vectors during the virus infection process. In the proposed model, five compartments were considered, namely, susceptible individuals, exposed individuals, infected individuals, recovered individuals, and environmental vectors (contaminated with free virus particles). In particular, the re-positive factor was taken into account (i.e., recovered individuals who have lost sufficient immune protection may still return to the exposed class). With the basic reproduction number R0 of the model, the global stability of the disease-free equilibrium and uniform persistence of the model were completely analyzed. Furthermore, sufficient conditions for the global stability of the endemic equilibrium of the model were also given. Finally, the effective predictability of the model was tested by fitting COVID-19 data from Japan and Italy. Full article
(This article belongs to the Special Issue Mathematical Modeling of the COVID-19 Pandemic)
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12 pages, 3730 KiB  
Article
Pathogenicity of GI-23 Avian Infectious Bronchitis Virus Strain Isolated in Brazil
by Iara Maria Trevisol, Luizinho Caron, Marcos Antônio Zanella Mores, Daiane Voss-Rech, Gabriel da Silva Zani, Alberto Back, Jorge Augusto Petroli Marchesi and Paulo Augusto Esteves
Viruses 2023, 15(5), 1200; https://doi.org/10.3390/v15051200 - 19 May 2023
Cited by 2 | Viewed by 1643
Abstract
IBV variants belonging to the GI-23 lineage have circulated since 1998 in the Middle East and have spread to several countries over time. In Brazil, the first report of GI-23 occurred in 2022. The study aimed to evaluate the in vivo pathogenicity of [...] Read more.
IBV variants belonging to the GI-23 lineage have circulated since 1998 in the Middle East and have spread to several countries over time. In Brazil, the first report of GI-23 occurred in 2022. The study aimed to evaluate the in vivo pathogenicity of exotic variant GI-23 isolates. Biological samples were screening by real-time RT-PCR and classified in to GI-1 or G1-11 lineages. Interestingly, 47.77% were not classified in these lineages. Nine of the unclassified strains were sequenced and showed a high similarity to the GI-23 strain. All nine were isolated and three, were studied for pathogenicity. At necropsy, the main observations were the presence of mucus in the trachea and congestion in the tracheal mucosa. In addition, lesions on the tracheas showed marked ciliostasis, and the ciliary activity confirmed the high pathogenicity of isolates. This variant is highly pathogenic to the upper respiratory tract and can cause severe kidney lesions. This study confirm a circulation of GI-23 strain in the country and report, to first time, the isolation of an exotic variant of IBV in Brazil. Full article
(This article belongs to the Special Issue Infectious Bronchitis Virus)
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17 pages, 2198 KiB  
Article
Efficacy of Remdesivir and Neutralizing Monoclonal Antibodies in Monotherapy or Combination Therapy in Reducing the Risk of Disease Progression in Elderly or Immunocompromised Hosts Hospitalized for COVID-19: A Single Center Retrospective Study
by Davide Fiore Bavaro, Lucia Diella, Alessandra Belati, Giuliana Metrangolo, Laura De Santis, Vito Spada, Michele Camporeale, Angelo Dargenio, Gaetano Brindicci, Flavia Balena, Deborah Fiordelisi, Fabio Signorile, Giacomo Loseto, Crescenza Pasciolla, Carla Minoia, Immacolata Attolico, Tommasina Perrone, Simona Simone, Maria Rendina, Nicoletta Giovine, Francesco Di Gennaro, Pellegrino Musto, Attilio Guarini, Alfredo Di Leo, Loreto Gesualdo, Maria Dell’Aera and Annalisa Saracinoadd Show full author list remove Hide full author list
Viruses 2023, 15(5), 1199; https://doi.org/10.3390/v15051199 - 19 May 2023
Cited by 3 | Viewed by 1454
Abstract
Introduction: Remdesivir (REM) and monoclonal antibodies (mAbs) could alleviate severe COVID-19 in at-risk outpatients. However, data on their use in hospitalized patients, particularly in elderly or immunocompromised hosts, are lacking. Methods: All consecutive patients hospitalized with COVID-19 at our unit from 1 July [...] Read more.
Introduction: Remdesivir (REM) and monoclonal antibodies (mAbs) could alleviate severe COVID-19 in at-risk outpatients. However, data on their use in hospitalized patients, particularly in elderly or immunocompromised hosts, are lacking. Methods: All consecutive patients hospitalized with COVID-19 at our unit from 1 July 2021 to 15 March 2022 were retrospectively enrolled. The primary outcome was the progression to severe COVID-19 (P/F < 200). Descriptive statistics, a Cox univariate–multivariate model, and an inverse probability treatment-weighted (IPTW) analysis were performed. Results: Overall, 331 subjects were included; their median (q1–q3) age was 71 (51–80) years, and they were males in 52% of the cases. Of them, 78 (23%) developed severe COVID-19. All-cause in-hospital mortality was 14%; it was higher in those with disease progression (36% vs. 7%, p < 0.001). REM and mAbs resulted in a 7% (95%CI = 3–11%) and 14% (95%CI = 3–25%) reduction in the risk of severe COVID-19, respectively, after adjusting the analysis with the IPTW. In addition, by evaluating only immunocompromised hosts, the combination of REM and mAbs was associated with a significantly lower incidence of severe COVID-19 (aHR = 0.06, 95%CI = 0.02–0.77) when compared with monotherapy. Conclusions: REM and mAbs may reduce the risk of COVID-19 progression in hospitalized patients. Importantly, in immunocompromised hosts, the combination of mAbs and REM may be beneficial. Full article
(This article belongs to the Special Issue COVID-19 Pharmacotherapy)
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16 pages, 2911 KiB  
Article
Efficiency of Interferon-γ in Activating Dendritic Cells and Its Potential Synergy with Toll-like Receptor Agonists
by Yuanzhi Bian, Debra L. Walter and Chenming Zhang
Viruses 2023, 15(5), 1198; https://doi.org/10.3390/v15051198 - 19 May 2023
Cited by 4 | Viewed by 1495
Abstract
Interferon-γ (IFN-γ) is a cytokine that plays an important role in immune regulation, especially in the activation and differentiation of immune cells. Toll-like receptors (TLRs) are a family of pattern-recognition receptors that sense structural motifs related to pathogens and alert immune cells to [...] Read more.
Interferon-γ (IFN-γ) is a cytokine that plays an important role in immune regulation, especially in the activation and differentiation of immune cells. Toll-like receptors (TLRs) are a family of pattern-recognition receptors that sense structural motifs related to pathogens and alert immune cells to the invasion. Both IFN-γ and TLR agonists have been used as immunoadjuvants to augment the efficacy of cancer immunotherapies and vaccines against infectious diseases or psychoactive compounds. In this study, we aimed to explore the potential of IFN-γ and TLR agonists being applied simultaneously to boost dendritic cell activation and the subsequent antigen presentation. In brief, murine dendritic cells were treated with IFN-γ and/or the TLR agonists, polyinosinic–polycytidylic acid (poly I:C), or resiquimod (R848). Next, the dendritic cells were stained for an activation marker, a cluster of differentiation 86 (CD86), and the percentage of CD86-positive cells was measured by flow cytometry. From the cytometric analysis, IFN-γ efficiently stimulated a considerable number of the dendritic cells, while the TLR agonists by themselves could merely activate a few compared to the control. The combination of IFN-γ with poly I:C or R848 triggered a higher amount of dendritic cell activation than IFN-γ alone. For instance, 10 ng/mL IFN-γ with 100 µg/mL poly I:C achieved 59.1% cell activation, which was significantly higher than the 33.4% CD86-positive cells obtained by 10 ng/mL IFN-γ. These results suggested that IFN-γ and TLR agonists could be applied as complementary systems to promote dendritic cell activation and antigen presentation. There might be a synergy between the two classes of molecules, but further investigation is warranted to ascertain the interaction of their promotive activities. Full article
(This article belongs to the Special Issue Biologics for Emerging and Reemerging Viral Infections)
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8 pages, 280 KiB  
Communication
Association of Polymorphisms of IL-6 Pathway Genes (IL6, IL6R and IL6ST) with COVID-19 Severity in an Amazonian Population
by Fabíola Brasil Barbosa Rodrigues, Rosilene da Silva, Erika Ferreira dos Santos, Mioni Thieli Figueiredo Magalhães de Brito, Andréa Luciana Soares da Silva, Mauro de Meira Leite, Flávia Póvoa da Costa, Maria de Nazaré do Socorro de Almeida Viana, Kevin Matheus Lima de Sarges, Marcos Henrique Damasceno Cantanhede, Adriana de Oliveira Lameira Veríssimo, Mayara da Silva Carvalho, Daniele Freitas Henriques, Carla Pinheiro da Silva, Igor Brasil Costa, Juliana Abreu Lima Nunes, Iran Barros Costa, Giselle Maria Rachid Viana, Maria Alice Freitas Queiroz, Sandra Souza Lima, Jeferson da Costa Lopes, Maria Karoliny da Silva Torres, Izaura Maria Vieira Cayres Vallinoto, Carlos David Araújo Bichara, Antonio Carlos Rosário Vallinoto and Eduardo José Melo dos Santosadd Show full author list remove Hide full author list
Viruses 2023, 15(5), 1197; https://doi.org/10.3390/v15051197 - 19 May 2023
Cited by 2 | Viewed by 1129
Abstract
Interleukin-6 has been recognized as a major role player in COVID-19 severity, being an important regulator of the cytokine storm. Hence, the evaluation of the influence of polymorphisms in key genes of the IL-6 pathway, namely IL6, IL6R, and IL6ST, may provide valuable [...] Read more.
Interleukin-6 has been recognized as a major role player in COVID-19 severity, being an important regulator of the cytokine storm. Hence, the evaluation of the influence of polymorphisms in key genes of the IL-6 pathway, namely IL6, IL6R, and IL6ST, may provide valuable prognostic/predictive markers for COVID-19. The present cross-sectional study genotyped three SNPs (rs1800795, rs2228145, and rs7730934) at IL6. IL6R and IL6ST genes, respectively, in 227 COVID-19 patients (132 hospitalized and 95 non-hospitalized). Genotype frequencies were compared between these groups. As a control group, published data on gene and genotype frequencies were gathered from published studies before the pandemic started. Our major results point to an association of the IL6 C allele with COVID-19 severity. Moreover, IL-6 plasmatic levels were higher among IL6 CC genotype carriers. Additionally, the frequency of symptoms was higher at IL6 CC and IL6R CC genotypes. In conclusion, the data suggest an important role of IL6 C allele and IL6R CC genotype on COVID-19 severity, in agreement with indirect evidence from the literature about the association of these genotypes with mortality rates, pneumonia, and heightening of protein plasmatic levels pro-inflammatory driven effects. Full article
(This article belongs to the Special Issue Cytokines in SARS-CoV-2 Infection)
16 pages, 3302 KiB  
Article
Inference of the Life Cycle of Environmental Phages from Genomic Signature Distances to Their Hosts
by Vicente Arnau, Wladimiro Díaz-Villanueva, Jorge Mifsut Benet, Paula Villasante, Beatriz Beamud, Paula Mompó, Rafael Sanjuan, Fernando González-Candelas, Pilar Domingo-Calap and Mária Džunková
Viruses 2023, 15(5), 1196; https://doi.org/10.3390/v15051196 - 19 May 2023
Cited by 2 | Viewed by 2119
Abstract
The environmental impact of uncultured phages is shaped by their preferred life cycle (lytic or lysogenic). However, our ability to predict it is very limited. We aimed to discriminate between lytic and lysogenic phages by comparing the similarity of their genomic signatures to [...] Read more.
The environmental impact of uncultured phages is shaped by their preferred life cycle (lytic or lysogenic). However, our ability to predict it is very limited. We aimed to discriminate between lytic and lysogenic phages by comparing the similarity of their genomic signatures to those of their hosts, reflecting their co-evolution. We tested two approaches: (1) similarities of tetramer relative frequencies, (2) alignment-free comparisons based on exact k = 14 oligonucleotide matches. First, we explored 5126 reference bacterial host strains and 284 associated phages and found an approximate threshold for distinguishing lysogenic and lytic phages using both oligonucleotide-based methods. The analysis of 6482 plasmids revealed the potential for horizontal gene transfer between different host genera and, in some cases, distant bacterial taxa. Subsequently, we experimentally analyzed combinations of 138 Klebsiella pneumoniae strains and their 41 phages and found that the phages with the largest number of interactions with these strains in the laboratory had the shortest genomic distances to K. pneumoniae. We then applied our methods to 24 single-cells from a hot spring biofilm containing 41 uncultured phage–host pairs, and the results were compatible with the lysogenic life cycle of phages detected in this environment. In conclusion, oligonucleotide-based genome analysis methods can be used for predictions of (1) life cycles of environmental phages, (2) phages with the broadest host range in culture collections, and (3) potential horizontal gene transfer by plasmids. Full article
(This article belongs to the Special Issue Phage–Host Interactions: From Communities to Single Particles)
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18 pages, 7986 KiB  
Article
Canocapavir Is a Novel Capsid Assembly Modulator Inducing a Conformational Change of the Linker Region of HBV Core Protein
by Yuan Zheng, Le Yang, Lin Yu, Yuanfei Zhu, Yang Wu, Zhijun Zhang, Tian Xia and Qiang Deng
Viruses 2023, 15(5), 1195; https://doi.org/10.3390/v15051195 - 18 May 2023
Cited by 2 | Viewed by 1530
Abstract
Canocapavir is a novel antiviral agent with characteristics of core protein allosteric modulators (CpAMs) that is currently in a phase II clinical trial for treatment of hepatitis B virus (HBV) infection. Herein, we show that Canocapavir prevented the encapsidation of HBV pregenomic RNA [...] Read more.
Canocapavir is a novel antiviral agent with characteristics of core protein allosteric modulators (CpAMs) that is currently in a phase II clinical trial for treatment of hepatitis B virus (HBV) infection. Herein, we show that Canocapavir prevented the encapsidation of HBV pregenomic RNA and increased the accumulation of cytoplasmic empty capsids, presumably by targeting the hydrophobic pocket at the dimer-dimer interface of HBV core protein (HBc). Canocapavir treatment markedly reduced the egress of naked capsids, which could be reversed by Alix overexpression through a mechanism other than direct association of Alix with HBc. Moreover, Canocapavir interfered with the interaction between HBc and HBV large surface protein, resulting in diminished production of empty virions. Of particular note, Canocapavir induced a conformational change of capsids, with the C-terminus of HBc linker region fully exposed on the exterior of capsids. We posit that the allosteric effect may have great importance in the anti-HBV activity of Canocapavir, given the emerging virological significance of HBc linker region. In support of this notion, the mutation at HBc V124W typically recapitulated the conformational change of the empty capsid with aberrant cytoplasmic accumulation. Collectively, our results indicate Canocapavir as a mechanistically distinct type of CpAMs against HBV infection. Full article
(This article belongs to the Special Issue Pathophysiology of Viral Hepatitis)
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17 pages, 1886 KiB  
Article
Molecular Epidemiology of SARS-CoV-2 during Five COVID-19 Waves and the Significance of Low-Frequency Lineages
by Kathleen Subramoney, Nkhensani Mtileni, Jennifer Giandhari, Yeshnee Naidoo, Yajna Ramphal, Sureshnee Pillay, Upasana Ramphal, Akhil Maharaj, Derek Tshiabuila, Houriiyah Tegally, Eduan Wilkinson, Tulio de Oliveira, Burtram C. Fielding and Florette K. Treurnicht
Viruses 2023, 15(5), 1194; https://doi.org/10.3390/v15051194 - 18 May 2023
Cited by 2 | Viewed by 1821 | Correction
Abstract
SARS-CoV-2 lineages and variants of concern (VOC) have gained more efficient transmission and immune evasion properties with time. We describe the circulation of VOCs in South Africa and the potential role of low-frequency lineages on the emergence of future lineages. Whole genome sequencing [...] Read more.
SARS-CoV-2 lineages and variants of concern (VOC) have gained more efficient transmission and immune evasion properties with time. We describe the circulation of VOCs in South Africa and the potential role of low-frequency lineages on the emergence of future lineages. Whole genome sequencing was performed on SARS-CoV-2 samples from South Africa. Sequences were analysed with Nextstrain pangolin tools and Stanford University Coronavirus Antiviral & Resistance Database. In 2020, 24 lineages were detected, with B.1 (3%; 8/278), B.1.1 (16%; 45/278), B.1.1.348 (3%; 8/278), B.1.1.52 (5%; 13/278), C.1 (13%; 37/278) and C.2 (2%; 6/278) circulating during the first wave. Beta emerged late in 2020, dominating the second wave of infection. B.1 and B.1.1 continued to circulate at low frequencies in 2021 and B.1.1 re-emerged in 2022. Beta was outcompeted by Delta in 2021, which was thereafter outcompeted by Omicron sub-lineages during the 4th and 5th waves in 2022. Several significant mutations identified in VOCs were also detected in low-frequency lineages, including S68F (E protein); I82T (M protein); P13L, R203K and G204R/K (N protein); R126S (ORF3a); P323L (RdRp); and N501Y, E484K, D614G, H655Y and N679K (S protein). Low-frequency variants, together with VOCs circulating, may lead to convergence and the emergence of future lineages that may increase transmissibility, infectivity and escape vaccine-induced or natural host immunity. Full article
(This article belongs to the Section SARS-CoV-2 and COVID-19)
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19 pages, 9204 KiB  
Article
Quantitative Mutation Analysis of Genes and Proteins of Major SARS-CoV-2 Variants of Concern and Interest
by Fengyi Liang
Viruses 2023, 15(5), 1193; https://doi.org/10.3390/v15051193 - 18 May 2023
Cited by 2 | Viewed by 1355
Abstract
Of various SARS-CoV-2 variants, some have drawn special concern or interest because of their heightened disease threat. The mutability of individual SARS-CoV-2 genes/proteins presumably varies. The present study quantified gene/protein mutations in 13 major SARS-CoV-2 variants of concern/interest, and analyzed viral protein antigenicity [...] Read more.
Of various SARS-CoV-2 variants, some have drawn special concern or interest because of their heightened disease threat. The mutability of individual SARS-CoV-2 genes/proteins presumably varies. The present study quantified gene/protein mutations in 13 major SARS-CoV-2 variants of concern/interest, and analyzed viral protein antigenicity using bioinformatics. The results from 187 carefully perused genome clones showed significantly higher mean percent mutations in the spike, ORF8, nucleocapsid, and NSP6 than in other viral proteins. The ORF8 and spike proteins also tolerated higher maximal percent mutations. The omicron variant presented more percent mutations in the NSP6 and structural proteins, whereas the delta featured more in the ORF7a. Omicron subvariant BA.2 exhibited more mutations in ORF6, and omicron BA.4 had more in NSP1, ORF6, and ORF7b, relative to omicron BA.1. Delta subvariants AY.4 and AY.5 bore more mutations in ORF7b and ORF8 than delta B.1.617.2. Predicted antigen ratios of SARS-CoV-2 proteins significantly vary (range: 38–88%). To overcome SARS-CoV-2 immune evasion, the relatively conserved, potentially immunogenic NSP4, NSP13, NSP14, membrane, and ORF3a viral proteins may serve as more suitable targets for molecular vaccines or therapeutics than the mutation-prone NSP6, spike, ORF8, or nucleocapsid protein. Further investigation into distinct mutations of the variants/subvariants may help understand SARS-CoV-2 pathogenesis. Full article
(This article belongs to the Section SARS-CoV-2 and COVID-19)
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15 pages, 10124 KiB  
Article
Generation and Characterization of a Replication-Competent Human Adenovirus Type 55 Encoding EGFP
by Wei Li, Yuehong Chen, Ye Feng, Jing Li, Xiaoping Kang, Sen Zhang, Yuchang Li, Zhiyan Zhao, Wenguang Yang, Lu Zhao, Huiyao Wang and Tao Jiang
Viruses 2023, 15(5), 1192; https://doi.org/10.3390/v15051192 - 18 May 2023
Cited by 1 | Viewed by 1381
Abstract
Human adenovirus 55 (HAdV-55) has recently caused outbreaks of acute respiratory disease (ARD), posing a significant public threat to civilians and military trainees. Efforts to develop antiviral inhibitors and quantify neutralizing antibodies require an experimental system to rapidly monitor viral infections, which can [...] Read more.
Human adenovirus 55 (HAdV-55) has recently caused outbreaks of acute respiratory disease (ARD), posing a significant public threat to civilians and military trainees. Efforts to develop antiviral inhibitors and quantify neutralizing antibodies require an experimental system to rapidly monitor viral infections, which can be achieved through the use of a plasmid that can produce an infectious virus. Here, we used a bacteria-mediated recombination approach to construct a full-length infectious cDNA clone, pAd55-FL, containing the whole genome of HadV-55. Then, the green fluorescent protein expression cassette was assembled into pAd55-FL to replace the E3 region to obtain a recombinant plasmid of pAd55-dE3-EGFP. The rescued recombinant virus rAdv55-dE3-EGFP is genetically stable and replicates similarly to the wild-type virus in cell culture. The virus rAdv55-dE3-EGFP can be used to quantify neutralizing antibody activity in sera samples, producing results in concordance with the cytopathic effect (CPE)-based microneutralization assay. Using an rAdv55-dE3-EGFP infection of A549 cells, we showed that the assay could be used for antiviral screening. Our findings suggest that the rAdv55-dE3-EGFP-based high-throughput assay provides a reliable tool for rapid neutralization testing and antiviral screening for HAdV-55. Full article
(This article belongs to the Special Issue Research and Clinical Application of Adenovirus (AdV))
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18 pages, 3738 KiB  
Article
Micro-CT Features of Lung Consolidation, Collagen Deposition and Inflammation in Experimental RSV Infection Are Aggravated in the Absence of Nrf2
by Teodora Ivanciuc, Igor Patrikeev, Yue Qu, Massoud Motamedi, Yava Jones-Hall, Antonella Casola and Roberto P. Garofalo
Viruses 2023, 15(5), 1191; https://doi.org/10.3390/v15051191 - 18 May 2023
Cited by 1 | Viewed by 1445
Abstract
Severe respiratory syncytial virus (RSV) infections in early life have been linked to the development of chronic airway disease. RSV triggers the production of reactive oxygen species (ROS), which contributes to inflammation and enhanced clinical disease. NF-E2-related factor 2 (Nrf2) is an important [...] Read more.
Severe respiratory syncytial virus (RSV) infections in early life have been linked to the development of chronic airway disease. RSV triggers the production of reactive oxygen species (ROS), which contributes to inflammation and enhanced clinical disease. NF-E2-related factor 2 (Nrf2) is an important redox-responsive protein that helps to protect cells and whole organisms from oxidative stress and injury. The role of Nrf2 in the context of viral-mediated chronic lung injury is not known. Herein, we show that RSV experimental infection of adult Nrf2-deficient BALB/c mice (Nrf2−/−; Nrf2 KO) is characterized by enhanced disease, increased inflammatory cell recruitment to the bronchoalveolar compartment and a more robust upregulation of innate and inflammatory genes and proteins, compared to wild-type Nrf2+/+ competent mice (WT). These events that occur at very early time points lead to increased peak RSV replication in Nrf2 KO compared to WT mice (day 5). To evaluate longitudinal changes in the lung architecture, mice were scanned weekly via high-resolution micro-computed tomography (micro-CT) imaging up to 28 days after initial viral inoculation. Based on micro-CT qualitative 2D imaging and quantitative reconstructed histogram-based analysis of lung volume and density, we found that RSV-infected Nrf2 KO mice developed significantly greater and prolonged fibrosis compared to WT mice. The results of this study underscore the critical role of Nrf2-mediated protection from oxidative injury, not only in the acute pathogenesis of RSV infection but also in the long-term consequences of chronic airway injury. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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1 pages, 161 KiB  
Correction
Correction: Gladkikh et al. Epidemiological Features of COVID-19 in Northwest Russia in 2021. Viruses 2022, 14, 931
by Anna Gladkikh, Vladimir Dedkov, Alena Sharova, Ekaterina Klyuchnikova, Valeriya Sbarzaglia, Olga Kanaeva, Tatyana Arbuzova, Nadezhda Tsyganova, Anna Popova, Edward Ramsay and Areg Totolian
Viruses 2023, 15(5), 1190; https://doi.org/10.3390/v15051190 - 18 May 2023
Viewed by 789
Abstract
There was an error in the original publication [...] Full article
(This article belongs to the Special Issue Viruses Research in Russia 2022)
13 pages, 1596 KiB  
Article
Temsavir Modulates HIV-1 Envelope Conformation by Decreasing Its Proteolytic Cleavage
by Marianne Boutin, Halima Medjahed, Manon Nayrac, Rishikesh Lotke, Gabrielle Gendron-Lepage, Catherine Bourassa, Daniel Sauter, Jonathan Richard and Andrés Finzi
Viruses 2023, 15(5), 1189; https://doi.org/10.3390/v15051189 - 18 May 2023
Cited by 1 | Viewed by 1326
Abstract
HIV-1 envelope glycoproteins (Envs) mediate viral entry and represent a target of choice for small molecule inhibitors. One of them, temsavir (BMS-626529) prevents the interaction of the host cell receptor CD4 with Env by binding the pocket under the β20–β21 loop of the [...] Read more.
HIV-1 envelope glycoproteins (Envs) mediate viral entry and represent a target of choice for small molecule inhibitors. One of them, temsavir (BMS-626529) prevents the interaction of the host cell receptor CD4 with Env by binding the pocket under the β20–β21 loop of the Env subunit gp120. Along with its capacity to prevent viral entry, temsavir stabilizes Env in its “closed” conformation. We recently reported that temsavir affects glycosylation, proteolytic processing, and overall conformation of Env. Here, we extend these results to a panel of primary Envs and infectious molecular clones (IMCs), where we observe a heterogeneous impact on Env cleavage and conformation. Our results suggest that the effect of temsavir on Env conformation is associated with its capacity to decrease Env processing. Indeed, we found that the effect of temsavir on Env processing affects the recognition of HIV-1-infected cells by broadly neutralizing antibodies and correlates with their capacity to mediate antibody-dependent cellular cytotoxicity (ADCC). Full article
(This article belongs to the Special Issue HIV-1 Entry Inhibitors)
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16 pages, 1592 KiB  
Article
Transcription Factor Driven Gene Regulation in COVID-19 Patients
by Daniele Santoni, Nimisha Ghosh, Carlo Derelitto and Indrajit Saha
Viruses 2023, 15(5), 1188; https://doi.org/10.3390/v15051188 - 18 May 2023
Cited by 1 | Viewed by 1279
Abstract
SARS-CoV-2 and its many variants have caused a worldwide emergency. Host cells colonised by SARS-CoV-2 present a significantly different gene expression landscape. As expected, this is particularly true for genes that directly interact with virus proteins. Thus, understanding the role that transcription factors [...] Read more.
SARS-CoV-2 and its many variants have caused a worldwide emergency. Host cells colonised by SARS-CoV-2 present a significantly different gene expression landscape. As expected, this is particularly true for genes that directly interact with virus proteins. Thus, understanding the role that transcription factors can play in driving differential regulation in patients affected by COVID-19 is a focal point to unveil virus infection. In this regard, we have identified 19 transcription factors which are predicted to target human proteins interacting with Spike glycoprotein of SARS-CoV-2. Transcriptomics RNA-Seq data derived from 13 human organs are used to analyse expression correlation between identified transcription factors and related target genes in both COVID-19 patients and healthy individuals. This resulted in the identification of transcription factors showing the most relevant impact in terms of most evident differential correlation between COVID-19 patients and healthy individuals. This analysis has also identified five organs such as the blood, heart, lung, nasopharynx and respiratory tract in which a major effect of differential regulation mediated by transcription factors is observed. These organs are also known to be affected by COVID-19, thereby providing consistency to our analysis. Furthermore, 31 key human genes differentially regulated by the transcription factors in the five organs are identified and the corresponding KEGG pathways and GO enrichment are also reported. Finally, the drugs targeting those 31 genes are also put forth. This in silico study explores the effects of transcription factors on human genes interacting with Spike glycoprotein of SARS-CoV-2 and intends to provide new insights to inhibit the virus infection. Full article
(This article belongs to the Special Issue Emerging Concepts in SARS-CoV-2 Biology and Pathology)
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