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Viruses, Volume 16, Issue 3 (March 2024) – 168 articles

Cover Story (view full-size image): Restriction factors constitute an important first-line defense of the host cell against viral infection. We demonstrate that cellular expression levels of the chromatin-remodeling factor SPOC1 (alternatively termed PHF13) critically determine the outcome of human cytomegalovirus infection. Our results suggest that SPOC1 exerts a multilayered defense strategy that increases the chromatin compaction of viral genes resulting in strongly diminished viral transcription, DNA replication and release. Furthermore, we provide evidence that this regulatory mechanism is supported by the polycomb repressive complex 2 and that association of these proteins with viral DNA might directly interfere with late viral transcription. View this paper
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13 pages, 1956 KiB  
Article
A Cocktail of Lipid Nanoparticle-mRNA Vaccines Broaden Immune Responses against β-Coronaviruses in a Murine Model
by Yi Zhang, Jialu Zhang, Dongmei Li, Qunying Mao, Xiuling Li, Zhenglun Liang and Qian He
Viruses 2024, 16(3), 484; https://doi.org/10.3390/v16030484 - 21 Mar 2024
Viewed by 900
Abstract
Severe acute respiratory syndrome (SARS)-coronavirus (CoV), Middle Eastern respiratory syndrome (MERS)-CoV, and SARS-CoV-2 have seriously threatened human life in the 21st century. Emerging and re-emerging β-coronaviruses after the coronavirus disease 2019 (COVID-19) epidemic remain possible highly pathogenic agents that can endanger human health. [...] Read more.
Severe acute respiratory syndrome (SARS)-coronavirus (CoV), Middle Eastern respiratory syndrome (MERS)-CoV, and SARS-CoV-2 have seriously threatened human life in the 21st century. Emerging and re-emerging β-coronaviruses after the coronavirus disease 2019 (COVID-19) epidemic remain possible highly pathogenic agents that can endanger human health. Thus, pan-β-coronavirus vaccine strategies to combat the upcoming dangers are urgently needed. In this study, four LNP-mRNA vaccines, named O, D, S, and M, targeting the spike protein of SARS-CoV-2 Omicron, Delta, SARS-CoV, and MERS-CoV, respectively, were synthesized and characterized for purity and integrity. All four LNP-mRNAs induced effective cellular and humoral immune responses against the corresponding spike protein antigens in mice. Furthermore, LNP-mRNA S and D induced neutralizing antibodies against SARS-CoV and SARS-CoV-2, which failed to cross-react with MERS-CoV. Subsequent evaluation of sequential and cocktail immunizations with LNP-mRNA O, D, S, and M effectively elicited broad immunity against SARS-CoV-2 variants, SARS-CoV, and MERS-CoV. A direct comparison of the sequential with cocktail regimens indicated that the cocktail vaccination strategy induced more potent neutralizing antibodies and T-cell responses against heterotypic viruses as well as broader antibody activity against pan-β-coronaviruses. Overall, these results present a potential pan-β-coronavirus vaccine strategy for improved preparedness prior to future coronavirus threats. Full article
(This article belongs to the Section Coronaviruses)
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32 pages, 2115 KiB  
Review
The Adaptive Immune Response against Bunyavirales
by Reem Alatrash and Bobby Brooke Herrera
Viruses 2024, 16(3), 483; https://doi.org/10.3390/v16030483 - 21 Mar 2024
Viewed by 1097
Abstract
The Bunyavirales order includes at least fourteen families with diverse but related viruses, which are transmitted to vertebrate hosts by arthropod or rodent vectors. These viruses are responsible for an increasing number of outbreaks worldwide and represent a threat to public health. Infection [...] Read more.
The Bunyavirales order includes at least fourteen families with diverse but related viruses, which are transmitted to vertebrate hosts by arthropod or rodent vectors. These viruses are responsible for an increasing number of outbreaks worldwide and represent a threat to public health. Infection in humans can be asymptomatic, or it may present with a range of conditions from a mild, febrile illness to severe hemorrhagic syndromes and/or neurological complications. There is a need to develop safe and effective vaccines, a process requiring better understanding of the adaptive immune responses involved during infection. This review highlights the most recent findings regarding T cell and antibody responses to the five Bunyavirales families with known human pathogens (Peribunyaviridae, Phenuiviridae, Hantaviridae, Nairoviridae, and Arenaviridae). Future studies that define and characterize mechanistic correlates of protection against Bunyavirales infections or disease will help inform the development of effective vaccines. Full article
(This article belongs to the Special Issue RNA Viruses and Antibody Response, 2nd Edition)
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12 pages, 928 KiB  
Article
Wastewater-Based Epidemiology for Viral Surveillance from an Endemic Perspective: Evidence and Challenges
by Marco Verani, Alessandra Pagani, Ileana Federigi, Giulia Lauretani, Nebiyu Tariku Atomsa, Virginia Rossi, Luca Viviani and Annalaura Carducci
Viruses 2024, 16(3), 482; https://doi.org/10.3390/v16030482 - 20 Mar 2024
Viewed by 928
Abstract
Wastewater-based epidemiology (WBE) is currently used to monitor not only the spread of the viral SARS-CoV-2 pandemic but also that of other viruses in endemic conditions, particularly in the absence of syndromic surveillance. The continuous monitoring of sewage requires high expenditure and significant [...] Read more.
Wastewater-based epidemiology (WBE) is currently used to monitor not only the spread of the viral SARS-CoV-2 pandemic but also that of other viruses in endemic conditions, particularly in the absence of syndromic surveillance. The continuous monitoring of sewage requires high expenditure and significant time investments, highlighting the need for standardized methods and structured monitoring strategies. In this context, we conducted weekly wastewater monitoring in northwestern Tuscany (Italy) and targeted human adenovirus (HAdV), norovirus genogroup II (NoVggII), enterovirus (EV), and SARS-CoV-2. Samples were collected at the entrances of treatment plants and concentrated using PEG/NaCl precipitation, and viral nucleic acids were extracted and detected through real-time reverse transcription qPCR. NoVggII was the most identified target (84.4%), followed by HAdV, SARS-CoV-2, and EV. Only HAdV and EV exhibited seasonal peaks in spring and summer. Compared with data that were previously collected in the same study area (from February 2021 to September 2021), the results for SARS-CoV-2 revealed a shift from an epidemic to an endemic pattern, at least in the region under investigation, which was likely due to viral mutations that led to the spreading of new variants with increased resistance to summer environmental conditions. In conclusion, using standardized methods and an efficient monitoring strategy, WBE proves valuable for viral surveillance in pandemic and epidemic scenarios, enabling the identification of temporal–local distribution patterns that are useful for making informed public health decisions. Full article
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17 pages, 8724 KiB  
Article
The Effect of Global Spread, Epidemiology, and Control Strategies on the Evolution of the GI-19 Lineage of Infectious Bronchitis Virus
by Giovanni Franzo, Giulia Faustini, Claudia Maria Tucciarone, Francesca Poletto, Francesca Tonellato, Mattia Cecchinato and Matteo Legnardi
Viruses 2024, 16(3), 481; https://doi.org/10.3390/v16030481 - 20 Mar 2024
Viewed by 659
Abstract
The GI-19 lineage of infectious bronchitis virus (IBV) has emerged as one of the most impactful, particularly in the “Old World”. Originating in China several decades ago, it has consistently spread and evolved, often forming independent clades in various areas and countries, each [...] Read more.
The GI-19 lineage of infectious bronchitis virus (IBV) has emerged as one of the most impactful, particularly in the “Old World”. Originating in China several decades ago, it has consistently spread and evolved, often forming independent clades in various areas and countries, each with distinct production systems and control strategies. This study leverages this scenario to explore how different environments may influence virus evolution. Through the analysis of the complete S1 sequence, four datasets were identified, comprising strains of monophyletic clades circulating in different continents or countries (e.g., Asia vs. Europe and China vs. Thailand), indicative of single introduction events and independent evolution. The population dynamics and evolutionary rate variation over time, as well as the presence and intensity of selective pressures, were estimated and compared across these datasets. Since the lineage origin (approximately in the mid-20th century), a more persistent and stable viral population was estimated in Asia and China, while in Europe and Thailand, a sharp increase following the introduction (i.e., 2005 and 2007, respectively) of GI-19 was observed, succeeded by a rapid decline. Although a greater number of sites on the S1 subunit were under diversifying selection in the Asian and Chinese datasets, more focused and stronger pressures were evident in both the European (positions 2, 52, 54, 222, and 379 and Thai (i.e., positions 10, 12, 32, 56, 62, 64, 65, 78, 95, 96, 119, 128, 140, 182, 292, 304, 320, and 323) strains, likely reflecting a more intense and uniform application of vaccines in these regions. This evidence, along with the analysis of control strategies implemented in different areas, suggests a strong link between effective, systematic vaccine implementation and infection control. However, while the overall evolutionary rate was estimated at approximately 10−3 to 10−4, a significant inverse correlation was found between viral population size and the rate of viral evolution over time. Therefore, despite the stronger selective pressure imposed by vaccination, effectively constraining the former through adequate control strategies can efficiently prevent viral evolution and the emergence of vaccine-escaping variants. Full article
(This article belongs to the Special Issue Evolution and Adaptation of Avian Viruses)
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9 pages, 1702 KiB  
Brief Report
Parvovirus B19 Outbreak in Israel: Retrospective Molecular Analysis from 2010 to 2023
by Orna Mor, Marina Wax, Shoshana-Shani Arami, Maya Yitzhaki, Or Kriger, Oran Erster and Neta S. Zuckerman
Viruses 2024, 16(3), 480; https://doi.org/10.3390/v16030480 - 20 Mar 2024
Viewed by 649
Abstract
This study presents an analysis of the epidemiological trends of parvovirus B19 (B19V) in Israel from 2010 to 2023, with particular emphasis on the outbreak in 2023. The analysis utilized molecular diagnostic data from individual patients obtained at the Central Virology Laboratory. Between [...] Read more.
This study presents an analysis of the epidemiological trends of parvovirus B19 (B19V) in Israel from 2010 to 2023, with particular emphasis on the outbreak in 2023. The analysis utilized molecular diagnostic data from individual patients obtained at the Central Virology Laboratory. Between 2010 and 2022, 8.5% of PCR-tested samples were positive for B19V, whereas in 2023, this percentage surged to 31% of PCR-tested samples. Throughout the study period, annual cycles consistently peaked in early spring/summer, with the most recent prominent outbreak occurring in 2016. Predominantly, diagnoses were made in children and women aged 20–39. Despite the notable surge in 2023, over 80% of positive cases continued to be observed in children and young women, with a decrease in cases during winter months. Furthermore, genotype 1a of the virus remained the predominant strain circulating during the outbreak. In light of these circumstances, consideration should be given to implementing screening measures, particularly among high-risk groups such as pregnant women. Full article
(This article belongs to the Special Issue Advances in Parvovirus Research 2024)
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13 pages, 1345 KiB  
Article
Predicting Vaccine Effectiveness for Hospitalization and Symptomatic Disease for Novel SARS-CoV-2 Variants Using Neutralizing Antibody Titers
by Billy J. Gardner and A. Marm Kilpatrick
Viruses 2024, 16(3), 479; https://doi.org/10.3390/v16030479 - 20 Mar 2024
Viewed by 824
Abstract
The emergence of new virus variants, including the Omicron variant (B.1.1.529) of SARS-CoV-2, can lead to reduced vaccine effectiveness (VE) and the need for new vaccines or vaccine doses if the extent of immune evasion is severe. Neutralizing antibody titers have been shown [...] Read more.
The emergence of new virus variants, including the Omicron variant (B.1.1.529) of SARS-CoV-2, can lead to reduced vaccine effectiveness (VE) and the need for new vaccines or vaccine doses if the extent of immune evasion is severe. Neutralizing antibody titers have been shown to be a correlate of protection for SARS-CoV-2 and other pathogens, and could be used to quickly estimate vaccine effectiveness for new variants. However, no model currently exists to provide precise VE estimates for a new variant against severe disease for SARS-CoV-2 using robust datasets from several populations. We developed predictive models for VE against COVID-19 symptomatic disease and hospitalization across a 54-fold range of mean neutralizing antibody titers. For two mRNA vaccines (mRNA-1273, BNT162b2), models fit without Omicron data predicted that infection with the BA.1 Omicron variant increased the risk of hospitalization 2.8–4.4-fold and increased the risk of symptomatic disease 1.7–4.2-fold compared to the Delta variant. Out-of-sample validation showed that model predictions were accurate; all predictions were within 10% of observed VE estimates and fell within the model prediction intervals. Predictive models using neutralizing antibody titers can provide rapid VE estimates, which can inform vaccine booster timing, vaccine design, and vaccine selection for new virus variants. Full article
(This article belongs to the Special Issue Evaluation of COVID-19 Booster Vaccine Effects)
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26 pages, 2206 KiB  
Review
Bacteriophage–Host Interactions and the Therapeutic Potential of Bacteriophages
by Leon M. T. Dicks and Wian Vermeulen
Viruses 2024, 16(3), 478; https://doi.org/10.3390/v16030478 - 20 Mar 2024
Viewed by 1356
Abstract
Healthcare faces a major problem with the increased emergence of antimicrobial resistance due to over-prescribing antibiotics. Bacteriophages may provide a solution to the treatment of bacterial infections given their specificity. Enzymes such as endolysins, exolysins, endopeptidases, endosialidases, and depolymerases produced by phages interact [...] Read more.
Healthcare faces a major problem with the increased emergence of antimicrobial resistance due to over-prescribing antibiotics. Bacteriophages may provide a solution to the treatment of bacterial infections given their specificity. Enzymes such as endolysins, exolysins, endopeptidases, endosialidases, and depolymerases produced by phages interact with bacterial surfaces, cell wall components, and exopolysaccharides, and may even destroy biofilms. Enzymatic cleavage of the host cell envelope components exposes specific receptors required for phage adhesion. Gram-positive bacteria are susceptible to phage infiltration through their peptidoglycan, cell wall teichoic acid (WTA), lipoteichoic acids (LTAs), and flagella. In Gram-negative bacteria, lipopolysaccharides (LPSs), pili, and capsules serve as targets. Defense mechanisms used by bacteria differ and include physical barriers (e.g., capsules) or endogenous mechanisms such as clustered regularly interspaced palindromic repeat (CRISPR)-associated protein (Cas) systems. Phage proteins stimulate immune responses against specific pathogens and improve antibiotic susceptibility. This review discusses the attachment of phages to bacterial cells, the penetration of bacterial cells, the use of phages in the treatment of bacterial infections, and the limitations of phage therapy. The therapeutic potential of phage-derived proteins and the impact that genomically engineered phages may have in the treatment of infections are summarized. Full article
(This article belongs to the Section Bacterial Viruses)
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15 pages, 3159 KiB  
Article
Predicting Natural Evolution in the RBD Region of the Spike Glycoprotein of SARS-CoV-2 by Machine Learning
by Yiheng Liu, Zitong He, Liyiyang Jia, Yiwei Xue, Yuxuan Du, Huiwen Tan, Xianzhi Zhang, Yu Ji, Yigang Tong, Haijun Xu and Luo Liu
Viruses 2024, 16(3), 477; https://doi.org/10.3390/v16030477 - 20 Mar 2024
Viewed by 739
Abstract
Machine learning (ML) is a key focus in predicting protein mutations and aiding directed evolution. Research on potential virus variants is crucial for vaccine development. In this study, the machine learning software PyPEF was employed to conduct mutation analysis within the receptor-binding domain [...] Read more.
Machine learning (ML) is a key focus in predicting protein mutations and aiding directed evolution. Research on potential virus variants is crucial for vaccine development. In this study, the machine learning software PyPEF was employed to conduct mutation analysis within the receptor-binding domain (RBD) of the Spike glycoprotein of SARS-CoV-2. Over 48,960,000 variants were predicted. Eight prospective variants that could surface in the future underwent modeling and molecular dynamics simulations. The study forecasts that the latest variant, ISOY2P5O1, may potentially emerge around 17 November 2023, with an approximate window of uncertainty of ±22 days. The ISOY8P5O2 variant displayed an increased binding capacity in the dry assay, with a total predicted binding energy of −110.306 kcal/mol. This represents an 8.25% enhancement in total binding energy compared to the original SARS-CoV-2 strain discovered in Wuhan (−101.892 kcal/mol). Reverse research confirmed the structural significance of mutation sites using ML models, particularly in the context of protein folding. The study validated regression methods (SVR, RF, and PLS) with different data structures. This study investigates the effectiveness of the “ML-Guided Design Correctly Predicts Combinatorial Effects Strategy” compared to the “ML-Guided Design Correctly Predicts Natural Evolution Prediction Strategy”. To enhance machine learning, we created a timestamping algorithm and two auxiliary programs using advanced techniques to rapidly process extensive data, surpassing batch sequencing capabilities. This study not only advances machine learning in guiding protein evolution but also holds potential for forecasting future viruses and vaccine development. Full article
(This article belongs to the Special Issue Computational Modeling in RNA Viruses)
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9 pages, 912 KiB  
Communication
Epidemiological and Genetic Characterization of Coxsackievirus A6-Associated Hand, Foot, and Mouth Disease in Gwangju, South Korea, in 2022
by Ji-Eun Lee, Min-Ji Kim, Mi-Hyeon Lim, Sue-Ji Han, Jin-Yeong Kim, Soo-Hoo Kim, Yi-Duen Ha, Gyung-Li Gang, Yoon-Seok Chung and Jung-Mi Seo
Viruses 2024, 16(3), 476; https://doi.org/10.3390/v16030476 - 20 Mar 2024
Viewed by 814
Abstract
Coxsackievirus A6 (CV-A6) has emerged as the predominant causative agent of hand, foot, and mouth disease (HFMD) in young children. Since the declaration of coronavirus disease 2019 (COVID-19) as a global pandemic, the incidence of infectious diseases, including HFMD, has decreased markedly. When [...] Read more.
Coxsackievirus A6 (CV-A6) has emerged as the predominant causative agent of hand, foot, and mouth disease (HFMD) in young children. Since the declaration of coronavirus disease 2019 (COVID-19) as a global pandemic, the incidence of infectious diseases, including HFMD, has decreased markedly. When social mitigation was relaxed during the COVID-19 pandemic in 2022, the re-emergence of HFMD was observed in Gwangju, South Korea, and seasonal characteristics of the disease appeared to have changed. To investigate the molecular characteristics of enterovirus (EV) associated with HFMD during 2022, 277 specimens were collected. Children aged younger than 5 years accounted for the majority of affected individuals. EV detection and genotyping were performed using real-time RT-PCR and nested RT-PCR followed by sequence analysis. The EV detection rate was found to be 82.3%, and the main genotype identified was CV-A6. Sixteen CV-A6 samples were selected for whole genome sequencing. According to phylogenetic analysis, all CV-A6 strains from this study belonged to the sub-genotype D3 clade based on VP1 sequences. Analysis of 3D polymerase phylogeny showed that only the recombinant RF-A group was identified. In conclusion, circulating EV types should be continuously monitored to understand pathogen emergence and evolution during the post-pandemic era. Full article
(This article belongs to the Special Issue An Update on Enterovirus Research)
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10 pages, 1262 KiB  
Article
A New Inovirus from the Human Blood Encodes Proteins with Nuclear Subcellular Localization
by Nikolay Popgeorgiev, Mart Krupovic, Julien Hiblot, Laura Fancello, Sonia Monteil-Bouchard and Christelle Desnues
Viruses 2024, 16(3), 475; https://doi.org/10.3390/v16030475 - 20 Mar 2024
Viewed by 682
Abstract
Viruses infecting bacteria (bacteriophages) represent the most abundant viral particles in the human body. They participate in the control of the human-associated bacterial communities and play an important role in the dissemination of virulence genes. Here, we present the identification of a new [...] Read more.
Viruses infecting bacteria (bacteriophages) represent the most abundant viral particles in the human body. They participate in the control of the human-associated bacterial communities and play an important role in the dissemination of virulence genes. Here, we present the identification of a new filamentous single-stranded DNA phage of the family Inoviridae, named Ralstonia Inoviridae Phage 1 (RIP1), in the human blood. Metagenomics and PCR analyses detected the RIP1 genome in blood serum, in the absence of concomitant bacterial infection or contamination, suggesting inovirus persistence in the human blood. Finally, we have experimentally demonstrated that the RIP1-encoded rolling circle replication initiation protein and serine integrase have functional nuclear localization signals and upon expression in eukaryotic cells both proteins were translocated into the nucleus. This observation adds to the growing body of data suggesting that phages could have an overlooked impact on the evolution of eukaryotic cells. Full article
(This article belongs to the Special Issue Inoviruses)
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14 pages, 1211 KiB  
Review
A Balancing Act: The Viral–Host Battle over RNA Binding Proteins
by Yahaira Bermudez, David Hatfield and Mandy Muller
Viruses 2024, 16(3), 474; https://doi.org/10.3390/v16030474 - 20 Mar 2024
Viewed by 745
Abstract
A defining feature of a productive viral infection is the co-opting of host cell resources for viral replication. Despite the host repertoire of molecular functions and biological counter measures, viruses still subvert host defenses to take control of cellular factors such as RNA [...] Read more.
A defining feature of a productive viral infection is the co-opting of host cell resources for viral replication. Despite the host repertoire of molecular functions and biological counter measures, viruses still subvert host defenses to take control of cellular factors such as RNA binding proteins (RBPs). RBPs are involved in virtually all steps of mRNA life, forming ribonucleoprotein complexes (mRNPs) in a highly ordered and regulated process to control RNA fate and stability in the cell. As such, the hallmark of the viral takeover of a cell is the reshaping of RNA fate to modulate host gene expression and evade immune responses by altering RBP interactions. Here, we provide an extensive review of work in this area, particularly on the duality of the formation of RNP complexes that can be either pro- or antiviral. Overall, in this review, we highlight the various ways viruses co-opt RBPs to regulate RNA stability and modulate the outcome of infection by gathering novel insights gained from research studies in this field. Full article
(This article belongs to the Special Issue Regulation of the Virus Lifecycle by Cellular RNA-Binding Proteins)
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10 pages, 1924 KiB  
Brief Report
Cross-Reactivity Assessment of Vaccine-Derived SARS-CoV-2 T Cell Responses against BA.2.86 and JN.1
by Muhammad Saqib Sohail, Syed Faraz Ahmed, Ahmed Abdul Quadeer and Matthew R. McKay
Viruses 2024, 16(3), 473; https://doi.org/10.3390/v16030473 - 20 Mar 2024
Viewed by 889
Abstract
The SARS-CoV-2 Omicron sub-variants BA.2.86 and JN.1 contain multiple mutations in the spike protein that were not present in previous variants of concern and Omicron sub-variants. Preliminary research suggests that these variants reduce the neutralizing capability of antibodies induced by vaccines, which is [...] Read more.
The SARS-CoV-2 Omicron sub-variants BA.2.86 and JN.1 contain multiple mutations in the spike protein that were not present in previous variants of concern and Omicron sub-variants. Preliminary research suggests that these variants reduce the neutralizing capability of antibodies induced by vaccines, which is particularly significant for JN.1. This raises concern as many widely deployed COVID-19 vaccines are based on the spike protein of the ancestral Wuhan strain of SARS-CoV-2. While T cell responses have been shown to be robust against previous SARS-CoV-2 variants, less is known about the impact of mutations in BA.2.86 and JN.1 on T cell responses. We evaluate the effect of mutations specific to BA.2.86 and JN.1 on experimentally determined T cell epitopes derived from the spike protein of the ancestral Wuhan strain and the spike protein of the XBB.1.5 strain that has been recommended as a booster vaccine. Our data suggest that BA.2.86 and JN.1 affect numerous T cell epitopes in spike compared to previous variants; however, the widespread loss of T cell recognition against these variants is unlikely. Full article
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14 pages, 2506 KiB  
Article
An Evaluation of Type 1 Interferon Related Genes in Male and Female-Matched, SARS-CoV-2 Infected Individuals Early in the COVID-19 Pandemic
by Tom P. Huecksteadt, Elizabeth J. Myers, Samuel E. Aamodt, Shubhanshi Trivedi and Kristi J. Warren
Viruses 2024, 16(3), 472; https://doi.org/10.3390/v16030472 - 20 Mar 2024
Viewed by 807
Abstract
SARS-CoV-2 infection has claimed just over 1.1 million lives in the US since 2020. Globally, the SARS-CoV-2 respiratory infection spread to 771 million people and caused mortality in 6.9 million individuals to date. Much of the early literature showed that SARS-CoV-2 immunity was [...] Read more.
SARS-CoV-2 infection has claimed just over 1.1 million lives in the US since 2020. Globally, the SARS-CoV-2 respiratory infection spread to 771 million people and caused mortality in 6.9 million individuals to date. Much of the early literature showed that SARS-CoV-2 immunity was defective in the early stages of the pandemic, leading to heightened and, sometimes, chronic inflammatory responses in the lungs. This lung-associated ‘cytokine storm’ or ‘cytokine release syndrome’ led to the need for oxygen supplementation, respiratory distress syndrome, and mechanical ventilation in a relatively high number of people. In this study, we evaluated circulating PBMC from non-hospitalized, male and female, COVID-19+ individuals over the course of infection, from the day of diagnosis (day 0) to one-week post diagnosis (day 7), and finally 4 weeks after diagnosis (day 28). In our early studies, we included hospitalized and critically care patient PBMC; however, most of these individuals were lymphopenic, which limited our assessments of their immune integrity. We chose a panel of 30 interferon-stimulated genes (ISG) to evaluate by PCR and completed flow analysis for immune populations present in those PBMC. Lastly, we assessed immune activation by stimulating PBMC with common TLR ligands. We identified changes in innate cells, primarily the innate lymphoid cells (ILC, NK cells) and adaptive immune cells (CD4+ and CD8+ T cells) over this time course of infection. We found that the TLR-7 agonist, Resiquimod, and the TLR-4 ligand, LPS, induced significantly better IFNα and IFNγ responses in the later phase (day 28) of SARS-CoV-2 infection in those non-hospitalized COVID-19+ individuals as compared to early infection (day 0 and day 7). We concluded that TLR-7 and TLR-4 agonists may be effective adjuvants in COVID-19 vaccines for mounting immunity that is long-lasting against SARS-CoV-2 infection. Full article
(This article belongs to the Special Issue Lung Immunity to Respiratory Viruses)
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14 pages, 689 KiB  
Article
Investigation of the Correlation between Enterovirus Infection and the Climate Factor Complex Including the Ping-Year Factor and El Niño-Southern Oscillation in Taiwan
by Hsueh-Wen Yu, Chia-Hsuan Kuan, Liang-Wei Tseng, Hsing-Yu Chen, Meg-Yen Tsai and Yu-Sheng Chen
Viruses 2024, 16(3), 471; https://doi.org/10.3390/v16030471 - 20 Mar 2024
Viewed by 730
Abstract
Enterovirus infection and enterovirus infection with severe complications (EVSC) are critical issues in several aspects. However, there is no suitable predictive tool for these infections. A climate factor complex (CFC) containing several climate factors could provide more effective predictions. The ping-year factor (PYF) [...] Read more.
Enterovirus infection and enterovirus infection with severe complications (EVSC) are critical issues in several aspects. However, there is no suitable predictive tool for these infections. A climate factor complex (CFC) containing several climate factors could provide more effective predictions. The ping-year factor (PYF) and El Niño-Southern Oscillation (ENSO) are possible CFCs. This study aimed to determine the relationship between these two CFCs and the incidence of enterovirus infection. Children aged 15 years and younger with enterovirus infection and/or EVSC were enrolled between 2007 and 2022. Each year was categorized into a ping-year or non-ping-year according to the PYF. Poisson regression was used to evaluate the associations between the PYF, ENSO, and the incidence of enterovirus infection. Compared to the ping-year group, the incidence rate of enterovirus infection, the incidence rate of EVSC, and the ratio of EVSC in the non-ping-year group were 1.24, 3.38, and 2.73 times higher, respectively (p < 0.001). For every one-unit increase in La Niña, the incidence rate of enterovirus infection decreased to 0.96 times (p < 0.001). Our study indicated that CFCs could be potential predictors for enterovirus infection, and the PYF was more suitable than ENSO. Further research is needed to improve the predictive model. Full article
(This article belongs to the Special Issue An Update on Enterovirus Research)
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12 pages, 670 KiB  
Article
Development and Validation of Three Triplex Real-Time RT-PCR Assays for Typing African Horse Sickness Virus: Utility for Disease Control and Other Laboratory Applications
by Rubén Villalba, Cristina Tena-Tomás, María José Ruano, Marta Valero-Lorenzo, Ana López-Herranz, Cristina Cano-Gómez and Montserrat Agüero
Viruses 2024, 16(3), 470; https://doi.org/10.3390/v16030470 - 20 Mar 2024
Viewed by 606
Abstract
The African horse sickness virus (AHSV) belongs to the Genus Orbivirus, family Sedoreoviridae, and nine serotypes of the virus have been described to date. The AHSV genome is composed of ten linear segments of double-stranded (ds) RNA, numbered in decreasing size order (Seg-1 [...] Read more.
The African horse sickness virus (AHSV) belongs to the Genus Orbivirus, family Sedoreoviridae, and nine serotypes of the virus have been described to date. The AHSV genome is composed of ten linear segments of double-stranded (ds) RNA, numbered in decreasing size order (Seg-1 to Seg-10). Genome segment 2 (Seg-2) encodes outer-capsid protein VP2, the most variable AHSV protein and the primary target for neutralizing antibodies. Consequently, Seg-2 determines the identity of the virus serotype. An African horse sickness (AHS) outbreak in an AHS-free status country requires identifying the serotype as soon as possible to implement a serotype-specific vaccination program. Considering that nowadays ‘polyvalent live attenuated’ is the only commercially available vaccination strategy to control the disease, field and vaccine strains of different serotypes could co-circulate. Additionally, in AHS-endemic countries, more than one serotype is often circulating at the same time. Therefore, a strategy to rapidly determine the virus serotype in an AHS-positive sample is strongly recommended in both epidemiological situations. The main objective of this study is to describe the development and validation of three triplex real-time RT-PCR (rRT-PCR) methods for rapid AHSV serotype detection. Samples from recent AHS outbreaks in Kenia (2015–2017), Thailand (2020), and Nigeria (2023), and from the AHS outbreak in Spain (1987–1990), were included in the study for the validation of these methods. Full article
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13 pages, 1183 KiB  
Article
Trends of Hepatitis A Virus Infection in Poland: Assessing the Potential Impact of the COVID-19 Pandemic and War in Ukraine
by Piotr Rzymski, Dorota Zarębska-Michaluk, Agnieszka Genowska, Piotr Tyszko, Birute Strukcinskiene and Robert Flisiak
Viruses 2024, 16(3), 469; https://doi.org/10.3390/v16030469 - 20 Mar 2024
Viewed by 731
Abstract
Hepatitis A virus (HAV) is the most common cause of acute viral hepatitis, which is preventable by vaccination. This study analyzed trends of HAV infections in Poland according to socio-demographic features in the years 2009–2022 and assessed the potential impact of the COVID-19 [...] Read more.
Hepatitis A virus (HAV) is the most common cause of acute viral hepatitis, which is preventable by vaccination. This study analyzed trends of HAV infections in Poland according to socio-demographic features in the years 2009–2022 and assessed the potential impact of the COVID-19 pandemic (2020–2023) and the migration of war refugees from Ukraine (since February 2022). In 2009–2022, 7115 new cases of HAV infection were diagnosed in Poland, especially among men (66.4%) and in urban areas (77.4%). Infections among men were most common at the age of 25–34 (median rate 0.43 per 105) and in women aged 15–24 (median rate 0.39 per 105). Analysis of the 14-year frequency of HAV infections exhibited three trends, regardless of gender, age, and residence. The infections revealed a downward trend in 2009–2014, increased significantly in 2014–2018, and decreased again after 2018. A particularly rapid increase in HAV infections occurred between March 2017 and February 2018 (median rate 0.79 per 105). The high level of new infections persisted until the beginning of the COVID-19 pandemic, at which point it dropped significantly but did not reach the level recorded before March 2017. During the Omicron SARS-CoV-2 dominance period, the median rate of HAV infections was 0.053 per 105, with a four-fold increase being observed from February 2022 (when the migration of war refugees from Ukraine began) to August 2022. The presented results can serve as a reference point for further observations in Central Europe. The HAV epidemiological situation is unlikely to escalate in Poland but requires further monitoring. Full article
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19 pages, 749 KiB  
Review
Host-like RNA Elements Regulate Virus Translation
by Debjit Khan and Paul L. Fox
Viruses 2024, 16(3), 468; https://doi.org/10.3390/v16030468 - 20 Mar 2024
Viewed by 993
Abstract
Viruses are obligate, intracellular parasites that co-opt host cell machineries for propagation. Critical among these machineries are those that translate RNA into protein and their mechanisms of control. Most regulatory mechanisms effectuate their activity by targeting sequence or structural features at the RNA [...] Read more.
Viruses are obligate, intracellular parasites that co-opt host cell machineries for propagation. Critical among these machineries are those that translate RNA into protein and their mechanisms of control. Most regulatory mechanisms effectuate their activity by targeting sequence or structural features at the RNA termini, i.e., at the 5′ or 3′ ends, including the untranslated regions (UTRs). Translation of most eukaryotic mRNAs is initiated by 5′ cap-dependent scanning. In contrast, many viruses initiate translation at internal RNA regions at internal ribosome entry sites (IRESs). Eukaryotic mRNAs often contain upstream open reading frames (uORFs) that permit condition-dependent control of downstream major ORFs. To offset genome compression and increase coding capacity, some viruses take advantage of out-of-frame overlapping uORFs (oORFs). Lacking the essential machinery of protein synthesis, for example, ribosomes and other translation factors, all viruses utilize the host apparatus to generate virus protein. In addition, some viruses exhibit RNA elements that bind host regulatory factors that are not essential components of the translation machinery. SARS-CoV-2 is a paradigm example of a virus taking advantage of multiple features of eukaryotic host translation control: the virus mimics the established human GAIT regulatory element and co-opts four host aminoacyl tRNA synthetases to form a stimulatory binding complex. Utilizing discontinuous transcription, the elements are present and identical in all SARS-CoV-2 subgenomic RNAs (and the genomic RNA). Thus, the virus exhibits a post-transcriptional regulon that improves upon analogous eukaryotic regulons, in which a family of functionally related mRNA targets contain elements that are structurally similar but lacking sequence identity. This “thrifty” virus strategy can be exploited against the virus since targeting the element can suppress the expression of all subgenomic RNAs as well as the genomic RNA. Other 3′ end viral elements include 3′-cap-independent translation elements (3′-CITEs) and 3′-tRNA-like structures. Elucidation of virus translation control elements, their binding proteins, and their mechanisms can lead to novel therapeutic approaches to reduce virus replication and pathogenicity. Full article
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13 pages, 517 KiB  
Article
Assessing the Clinical Impact of the SARS-CoV-2 Gamma Variant on Intensive Care Unit Admissions: Insights from a Reference Hospital in Northeastern Brazil
by Carolina Kymie Vasques Nonaka, Adlas Michel de Jesus Ribeiro, Gisele Vieira Rocha, Helena Souza da Hora, Antônio Augusto Fonseca Junior, Fernanda de Macêdo Lima, Iasmin Nogueira Bastos, Samara Alves Sa Teles, Thamires Gomes Lopes Weber, Vanessa Ferreira Costa, Zaquer Suzana Costa-Ferro, Clarissa Araújo Gurgel Rocha, Silvia Inês Sardi, Gúbio Soares, Ana Verena Almeida Mendes and Bruno Solano de Freitas Souza
Viruses 2024, 16(3), 467; https://doi.org/10.3390/v16030467 - 20 Mar 2024
Viewed by 626
Abstract
The global challenge posed by the prolonged COVID-19 pandemic underscores the critical need for ongoing genomic surveillance to identify emerging variants and formulate effective public health strategies. This retrospective observational study, conducted in a reference hospital in Northeast Brazil and comprising 2116 cases, [...] Read more.
The global challenge posed by the prolonged COVID-19 pandemic underscores the critical need for ongoing genomic surveillance to identify emerging variants and formulate effective public health strategies. This retrospective observational study, conducted in a reference hospital in Northeast Brazil and comprising 2116 cases, employed PCR genotyping together with epidemiological data to elucidate the impact of the Gamma variant during its emergence, revealing distinct patterns in hospitalization rates, severity of illness, and outcomes. The study emphasizes the challenges posed by the variant, particularly an increased tendency for ICU admissions and respiratory support, especially among adults aged 18 to 59 without comorbidities. Laboratory analyses further demonstrate elevated inflammatory, coagulation, and hepatic markers in the Gamma variant cohort, suggesting a more severe systemic response. Despite limitations, including a retrospective approach and single-institution data, the study underscores the importance of ongoing genomic surveillance. Overall, this research contributes valuable insights into the impact of the Gamma variant on COVID-19 dynamics, advocating for continued research and surveillance to inform effective public health strategies regarding evolving viral variants. Full article
(This article belongs to the Special Issue Molecular Epidemiology of SARS-CoV-2: 2nd Edition)
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14 pages, 1447 KiB  
Article
Susceptibility of Mediterranean Buffalo (Bubalus bubalis) following Experimental Infection with Lumpy Skin Disease Virus
by Elisabetta Di Felice, Chiara Pinoni, Emanuela Rossi, Giorgia Amatori, Elisa Mancuso, Federica Iapaolo, Angela Taraschi, Giovanni Di Teodoro, Guido Di Donato, Gaetano Federico Ronchi, Maria Teresa Mercante, Mauro Di Ventura, Daniela Morelli and Federica Monaco
Viruses 2024, 16(3), 466; https://doi.org/10.3390/v16030466 - 19 Mar 2024
Viewed by 557
Abstract
Lumpy skin disease (LSD) is a viral disease of cattle and water buffalo characterized by cutaneous nodules, biphasic fever, and lymphadenitis. LSD is endemic in Africa and the Middle East but has spread to different Asian countries in recent years. The disease is [...] Read more.
Lumpy skin disease (LSD) is a viral disease of cattle and water buffalo characterized by cutaneous nodules, biphasic fever, and lymphadenitis. LSD is endemic in Africa and the Middle East but has spread to different Asian countries in recent years. The disease is well characterized in cattle while little is known about the disease in buffaloes in which no experimental studies have been conducted. Six buffaloes and two cattle were inoculated with an Albanian LSD virus (LSDV) field strain and clinically monitored for 42 days. Only two buffaloes showed fever, skin nodules, and lymphadenitis. All samples collected (blood, swabs, biopsies, and organs) were tested in real-time PCR and were negative. Between day 39 and day 42 after inoculation, anti-LSDV antibodies were detected in three buffaloes by ELISA, but all sera were negative by virus neutralization test (VNT). Cattle showed severe clinical signs, viremia, virus shedding proven by positive real-time PCR results, and seroconversion confirmed by both ELISA and VNT. Clinical findings suggest that susceptibility in buffaloes is limited compared to in cattle once experimentally infected with LSDV. Virological results support the hypothesis of buffalo resistance to LSD and its role as an accidental non-adapted host. This study highlights that the sensitivity of ELISA and VNT may differ between animal species and further studies are needed to investigate the epidemiological role of water buffalo. Full article
(This article belongs to the Special Issue Capripox Viruses: A Continuing Transboundary Threat to Animal Health)
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8 pages, 359 KiB  
Communication
Detection of Acipenser European Iridovirus (AcIV-E) in Sturgeon Farms in Northern Italy between 2021–2023
by Fabio Bondavalli, Dáša Schleicherová, Paolo Pastorino, Davide Mugetti, Claudio Pedron and Marino Prearo
Viruses 2024, 16(3), 465; https://doi.org/10.3390/v16030465 - 18 Mar 2024
Viewed by 549
Abstract
Sturgeon farming is rapidly expanding in Europe, where Italy ranks first in farmed caviar production. A major threat to sturgeon health in captivity is infection with Acipenser European Iridovirus (AcIV-E), a viral disease definitively identified in 2016. Here we present data on the [...] Read more.
Sturgeon farming is rapidly expanding in Europe, where Italy ranks first in farmed caviar production. A major threat to sturgeon health in captivity is infection with Acipenser European Iridovirus (AcIV-E), a viral disease definitively identified in 2016. Here we present data on the occurrence of AcIV-E in 482 sturgeons (age ≤ 12 months, species of the genus Acipenser and the species Huso huso) collected from sturgeon farms in northern Italy between January 2021 and December 2023. The health status of each specimen was determined by necroscopy and virological assay. Virological analysis was performed on gill samples and real-time PCR specific to the MCP gene of the iridovirus viral capsid. Molecular analysis revealed positivity to the virus in 204 samples (42.68% of the total), while anatomopathological examination of nearly all fish with positive real-time PCR disclosed swollen abdomen, hepatic steatosis, splenomegaly, and increased gill volume. Two challenges to timely diagnosis are the absence of pathognomonic symptoms and the inability to isolate the virus on cell monolayers. Continuous and widespread health monitoring is therefore crucial for disease management and to effectively control spread of the virus. Full article
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17 pages, 3141 KiB  
Article
Brincidofovir Effectively Inhibits Proliferation of Pseudorabies Virus by Disrupting Viral Replication
by Huihui Guo, Qingyun Liu, Dan Yang, Hao Zhang, Yan Kuang, Yafei Li, Huanchun Chen and Xiangru Wang
Viruses 2024, 16(3), 464; https://doi.org/10.3390/v16030464 - 18 Mar 2024
Viewed by 778
Abstract
Pseudorabies is an acute and febrile infectious disease caused by pseudorabies virus (PRV), a member of the family Herpesviridae. Currently, PRV is predominantly endemoepidemic and has caused significant economic losses among domestic pigs. Other animals have been proven to be susceptible to PRV, [...] Read more.
Pseudorabies is an acute and febrile infectious disease caused by pseudorabies virus (PRV), a member of the family Herpesviridae. Currently, PRV is predominantly endemoepidemic and has caused significant economic losses among domestic pigs. Other animals have been proven to be susceptible to PRV, with a mortality rate of 100%. In addition, 30 human cases of PRV infection have been reported in China since 2017, and all patients have shown severe neurological symptoms and eventually died or developed various neurological sequelae. In these cases, broad-spectrum anti-herpesvirus drugs and integrated treatments were mostly applied. However, the inhibitory effect of the commonly used anti-herpesvirus drugs (e.g., acyclovir, etc.) against PRV were evaluated and found to be limited in this study. It is therefore urgent and important to develop drugs that are clinically effective against PRV infection. Here, we constructed a high-throughput method for screening antiviral drugs based on fluorescence-tagged PRV strains and multi-modal microplate readers that detect fluorescence intensity to account for virus proliferation. A total of 2104 small molecule drugs approved by the U.S. Food and Drug Administration (FDA) were studied and validated by applying this screening model, and 104 drugs providing more than 75% inhibition of fluorescence intensity were selected. Furthermore, 10 drugs that could significantly inhibit PRV proliferation in vitro were strictly identified based on their cytopathic effects, virus titer, and viral gene expression, etc. Based on the determined 50% cytotoxic concentration (CC50) and 50% inhibitory concentration (IC50), the selectivity index (SI) was calculated to be 26.3–3937.2 for these 10 drugs, indicating excellent drugability. The antiviral effects of the 10 drugs were then assessed in a mouse model. It was found that 10 mg/kg brincidofovir administered continuously for 5 days provided 100% protection in mice challenged with lethal doses of the human-origin PRV strain hSD-1/2019. Brincidofovir significantly attenuated symptoms and pathological changes in infected mice. Additionally, time-of-addition experiments confirmed that brincidofovir inhibited the proliferation of PRV mainly by interfering with the viral replication stage. Therefore, this study confirms that brincidofovir can significantly inhibit PRV both in vitro and in vivo and is expected to be an effective drug candidate for the clinical treatment of PRV infections. Full article
(This article belongs to the Special Issue Pseudorabies Virus, Volume II)
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15 pages, 803 KiB  
Review
Acalculous Cholecystitis as a Complication of Primary Epstein-Barr Virus Infection: A Case-Based Scoping Review of the Literature
by Aristotelis Tsiakalos, Georgios Schinas, Aggelos Karatzaferis, Emmanouil Angelos Rigopoulos, Christos Pappas, Eleni Polyzou, Effrosyni Dimopoulou, George Dimopoulos and Karolina Akinosoglou
Viruses 2024, 16(3), 463; https://doi.org/10.3390/v16030463 - 18 Mar 2024
Viewed by 780
Abstract
Primary Epstein-Barr virus (EBV) infection manifests with diverse clinical symptoms, occasionally resulting in severe complications. This scoping review investigates the rare occurrence of acute acalculous cholecystitis (AAC) in the context of primary EBV infection, with a focus on understanding its prevalence, clinical features, [...] Read more.
Primary Epstein-Barr virus (EBV) infection manifests with diverse clinical symptoms, occasionally resulting in severe complications. This scoping review investigates the rare occurrence of acute acalculous cholecystitis (AAC) in the context of primary EBV infection, with a focus on understanding its prevalence, clinical features, and underlying mechanisms. The study also explores EBV infection association with Gilbert syndrome, a condition that potentially exacerbates the clinical picture. Additionally, a case report of an 18-year-old female presenting with AAC and ascites secondary to EBV infection enhances the review. A comprehensive literature review was conducted, analyzing reported cases of AAC secondary to EBV infection. This involved examining patient demographics, clinical presentations, laboratory findings, and outcomes. The search yielded 44 cases, predominantly affecting young females. Common clinical features included fever, cervical lymphadenopathy, tonsillitis/pharyngitis, and splenomegaly. Laboratory findings highlighted significant hepatic involvement. The review also noted a potential link between AAC in EBV infection and Gilbert syndrome, particularly in cases with abnormal bilirubin levels. AAC is a rare but significant complication of primary EBV infection, primarily observed in young females, and may be associated with Gilbert syndrome. This comprehensive review underscores the need for heightened clinical awareness and timely diagnosis to manage this complication effectively. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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21 pages, 48428 KiB  
Article
Serologic, Virologic and Pathologic Features of Cats with Naturally Occurring Feline Infectious Peritonitis Enrolled in Antiviral Clinical Trials
by Brian G. Murphy, Diego Castillo, N E Neely, Amir Kol, Terza Brostoff, Chris K. Grant and Krystle L. Reagan
Viruses 2024, 16(3), 462; https://doi.org/10.3390/v16030462 - 17 Mar 2024
Viewed by 1063
Abstract
Feline infectious peritonitis (FIP) is a multisystemic, generally lethal immuno-inflammatory disease of domestic cats caused by an infection with a genetic variant of feline coronavirus, referred to as the FIP virus (FIPV). We leveraged data from four different antiviral clinical trials performed at [...] Read more.
Feline infectious peritonitis (FIP) is a multisystemic, generally lethal immuno-inflammatory disease of domestic cats caused by an infection with a genetic variant of feline coronavirus, referred to as the FIP virus (FIPV). We leveraged data from four different antiviral clinical trials performed at the University of California, Davis. Collectively, a total of 60 client-owned domestic cats, each with a confirmed diagnosis of naturally occurring FIP, were treated with a variety of antiviral compounds. The tested therapies included the antiviral compounds GS-441524, remdesivir, molnupiravir and allogeneic feline mesenchymal stem/stroma cell transfusions. Four client-owned cats with FIP did not meet the inclusion criteria for the trials and were not treated with antiviral therapies; these cats were included in the data set as untreated FIP control cats. ELISA and Western blot assays were performed using feline serum/plasma or ascites effusions obtained from a subset of the FIP cats. Normalized tissue/effusion viral loads were determined in 34 cats by a quantitative RT-PCR of nucleic acids isolated from either effusions or abdominal lymph node tissue. Twenty-one cats were PCR “serotyped” (genotyped) and had the S1/S2 region of the coronaviral spike gene amplified, cloned and sequenced from effusions or abdominal lymph node tissue. In total, 3 untreated control cats and 14 (23.3%) of the 60 antiviral-treated cats died or were euthanized during (13) or after the completion of (1) antiviral treatment. Of these 17 cats, 13 had complete necropsies performed (10 cats treated with antivirals and 3 untreated control cats). We found that anticoronaviral serologic responses were persistent and robust throughout the treatment period, primarily the IgG isotype, and focused on the viral structural Nucleocapsid and Membrane proteins. Coronavirus serologic patterns were similar for the effusions and serum/plasma of cats with FIP and in cats entering remission or that died. Viral RNA was readily detectable in the majority of the cats in either abdominal lymph node tissue or ascites effusions, and all of the viral isolates were determined to be serotype I FIPV. Viral nucleic acids in cats treated with antiviral compounds became undetectable in ascites or abdominal lymph node tissue by 11 days post-treatment using a sensitive quantitative RT-PCR assay. The most common pathologic lesions identified in the necropsied cats were hepatitis, abdominal effusion (ascites), serositis, pancreatitis, lymphadenitis, icterus and perivasculitis. In cats treated with antiviral compounds, gross and histological lesions characteristic of FIP persisted for several weeks, while the viral antigen became progressively less detectable. Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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7 pages, 197 KiB  
Brief Report
Hereditary Connective Tissue Diseases and Risk of Post-Acute SARS-CoV-2
by Maggie L. Bartlett, Daniel Sova and Mahim Jain
Viruses 2024, 16(3), 461; https://doi.org/10.3390/v16030461 - 17 Mar 2024
Viewed by 693
Abstract
We completed a retrospective review of data collected by the JH-CROWN consortium based on ICD10 codes for a hospitalized cohort. The severity and prevalence of COVID-19 and development of PASC within heritable connective tissue diseases were unknown; however, clinical observation suggested a thorough [...] Read more.
We completed a retrospective review of data collected by the JH-CROWN consortium based on ICD10 codes for a hospitalized cohort. The severity and prevalence of COVID-19 and development of PASC within heritable connective tissue diseases were unknown; however, clinical observation suggested a thorough examination was necessary. We compared rates of disease severity, death, and PASC in connective tissue diseases versus the entire cohort as well as in diabetes and hypertension to determine if connective tissue disease was a risk factor. Of the 15,676 patients in the database, 63 (0.40%) had a connective tissue disease, which is elevated relative to the distribution in the population, suggesting a higher risk of severe disease. Within these 63 patients, 9.52% developed PASC compared to 2.54% in the entire cohort (p < 0.005). Elucidation of populations at high risk for severe disease and development of PASC is integral to improving treatment approaches. Further, no other study to date has examined the risk in those with connective tissue diseases and these data support a need for enhanced awareness among physicians, patients, and the community. Full article
(This article belongs to the Special Issue Viral Infections in Special Populations)
19 pages, 2387 KiB  
Article
A Novel Tiled Amplicon Sequencing Assay Targeting the Tomato Brown Rugose Fruit Virus (ToBRFV) Genome Reveals Widespread Distribution in Municipal Wastewater Treatment Systems in the Province of Ontario, Canada
by Delaney Nash, Isaac Ellmen, Jennifer J. Knapp, Ria Menon, Alyssa K. Overton, Jiujun Cheng, Michael D. J. Lynch, Jozef I. Nissimov and Trevor C. Charles
Viruses 2024, 16(3), 460; https://doi.org/10.3390/v16030460 - 17 Mar 2024
Viewed by 1003
Abstract
Tomato Brown Rugose Fruit Virus (ToBRFV) is a plant pathogen that infects important Solanaceae crop species and can dramatically reduce tomato crop yields. The ToBRFV has rapidly spread around the globe due to its ability to escape detection by antiviral host genes which [...] Read more.
Tomato Brown Rugose Fruit Virus (ToBRFV) is a plant pathogen that infects important Solanaceae crop species and can dramatically reduce tomato crop yields. The ToBRFV has rapidly spread around the globe due to its ability to escape detection by antiviral host genes which confer resistance to other tobamoviruses in tomato plants. The development of robust and reproducible methods for detecting viruses in the environment aids in the tracking and reduction of pathogen transmission. We detected ToBRFV in municipal wastewater influent (WWI) samples, likely due to its presence in human waste, demonstrating a widespread distribution of ToBRFV in WWI throughout Ontario, Canada. To aid in global ToBRFV surveillance efforts, we developed a tiled amplicon approach to sequence and track the evolution of ToBRFV genomes in municipal WWI. Our assay recovers 95.7% of the 6393 bp ToBRFV RefSeq genome, omitting the terminal 5′ and 3′ ends. We demonstrate that our sequencing assay is a robust, sensitive, and highly specific method for recovering ToBRFV genomes. Our ToBRFV assay was developed using existing ARTIC Network resources, including primer design, sequencing library prep, and read analysis. Additionally, we adapted our lineage abundance estimation tool, Alcov, to estimate the abundance of ToBRFV clades in samples. Full article
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0 pages, 600 KiB  
Review
Torque Teno Virus DNA Load in Blood as an Immune Status Biomarker in Adult Hematological Patients: The State of the Art and Future Prospects
by Eliseo Albert, Estela Giménez, Rafael Hernani, José Luis Piñana, Carlos Solano and David Navarro
Viruses 2024, 16(3), 459; https://doi.org/10.3390/v16030459 - 17 Mar 2024
Viewed by 684
Abstract
A solid body of scientific evidence supports the assumption that Torque teno virus (TTV) DNA load in the blood compartment may behave as a biomarker of immunosuppression in solid organ transplant recipients; in this clinical setting, high or increasing TTV DNA levels precede [...] Read more.
A solid body of scientific evidence supports the assumption that Torque teno virus (TTV) DNA load in the blood compartment may behave as a biomarker of immunosuppression in solid organ transplant recipients; in this clinical setting, high or increasing TTV DNA levels precede the occurrence of infectious complications, whereas the opposite anticipates the development of acute rejection. The potential clinical value of the TTV DNA load in blood to infer the risk of opportunistic viral infection or immune-related (i.e., graft vs. host disease) clinical events in the hematological patient, if any, remains to be determined. In fact, contradictory data have been published on this matter in the allo-SCT setting. Studies addressing this topic, which we review and discuss herein, are highly heterogeneous as regards design, patient characteristics, time points selected for TTV DNA load monitoring, and PCR assays used for TTV DNA quantification. Moreover, clinical outcomes are often poorly defined. Prospective, ideally multicenter, and sufficiently powered studies with well-defined clinical outcomes are warranted to elucidate whether TTV DNA load monitoring in blood may be of any clinical value in the management of hematological patients. Full article
(This article belongs to the Special Issue Advancing Research of Anelloviruses)
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14 pages, 1007 KiB  
Review
Insights from Avian Influenza: A Review of Its Multifaceted Nature and Future Pandemic Preparedness
by Jianning He and Yiu-Wing Kam
Viruses 2024, 16(3), 458; https://doi.org/10.3390/v16030458 - 17 Mar 2024
Viewed by 1608
Abstract
Avian influenza viruses (AIVs) have posed a significant pandemic threat since their discovery. This review mainly focuses on the epidemiology, virology, pathogenesis, and treatments of avian influenza viruses. We delve into the global spread, past pandemics, clinical symptoms, severity, and immune response related [...] Read more.
Avian influenza viruses (AIVs) have posed a significant pandemic threat since their discovery. This review mainly focuses on the epidemiology, virology, pathogenesis, and treatments of avian influenza viruses. We delve into the global spread, past pandemics, clinical symptoms, severity, and immune response related to AIVs. The review also discusses various control measures, including antiviral drugs, vaccines, and potential future directions in influenza treatment and prevention. Lastly, by summarizing the insights from previous pandemic control, this review aims to direct effective strategies for managing future influenza pandemics. Full article
(This article belongs to the Special Issue RNA Viruses and Antibody Response, 2nd Edition)
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10 pages, 1006 KiB  
Article
Determination of Optimal Antigen Yield and Virus Inactivation Conditions for the Production of the Candidate Foot-and-Mouth Disease Recombinant Vaccine Strain Asia1 Shamir-R in a Bioreactor
by Jae Young Kim, Sun Young Park, Gyeongmin Lee, Sang Hyun Park, Jong-Sook Jin, Dohyun Kim, Jong-Hyeon Park, Seong-Yun Jeong and Young-Joon Ko
Viruses 2024, 16(3), 457; https://doi.org/10.3390/v16030457 - 16 Mar 2024
Viewed by 670
Abstract
Since the foot-and-mouth disease (FMD) outbreak in South Korea in 2010–2011, vaccination policies utilizing inactivated FMD vaccines composed of types O and A have been implemented nationwide. However, because type Asia1 occurred in North Korea in 2007 and intermittently in neighboring countries, the [...] Read more.
Since the foot-and-mouth disease (FMD) outbreak in South Korea in 2010–2011, vaccination policies utilizing inactivated FMD vaccines composed of types O and A have been implemented nationwide. However, because type Asia1 occurred in North Korea in 2007 and intermittently in neighboring countries, the risk of type Asia1 introduction cannot be ruled out. This study evaluated the antigen yield and viral inactivation kinetics of the recombinant Asia1 Shamir vaccine strain (Asia1 Shamir-R). When Asia1 Shamir-R was proliferated in shaking flasks (1 L), a 2 L bioreactor (1 L), and a wave bioreactor (25 L), the antigen yields were 7.5 μg/mL, 5.2 μg/mL, and 3.8 μg/mL, respectively. The optimal FMDV inactivation conditions were 2 mM BEI at 26 °C and 1.0 mM BEI at 37 °C. There was no antigen loss due to BEI treatment, and only a decrease in antigen levels was observed during storage. The sera from pigs immunized with antigen derived from a bioreactor exhibited a neutralizing antibody titer of approximately 1/1000 against Asia1 Shamir and Asia1/MOG/05 viruses; therefore, Asia1 Shamir-R is expected to provide sufficient protection against both viruses. If an FMD vaccine production facility is established, this Asia1 Shamir-R can be employed for domestic antigen banks in South Korea. Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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7 pages, 497 KiB  
Brief Report
Direct Evidence of Powassan Virus Vertical Transmission in Ixodes scapularis in Nature
by Rachel E. Lange, Melissa A. Prusinski, Alan P. Dupuis II and Alexander T. Ciota
Viruses 2024, 16(3), 456; https://doi.org/10.3390/v16030456 - 16 Mar 2024
Viewed by 753
Abstract
Powassan virus (POWV) is a tick-borne flavivirus endemic in North America and Russia. Experimental infections with POWV have confirmed horizontal, transstadial, vertical, and cofeeding transmission routes for potential virus maintenance. In the field, vertical transmission has never been observed. During New York State [...] Read more.
Powassan virus (POWV) is a tick-borne flavivirus endemic in North America and Russia. Experimental infections with POWV have confirmed horizontal, transstadial, vertical, and cofeeding transmission routes for potential virus maintenance. In the field, vertical transmission has never been observed. During New York State tick-borne pathogen surveillance, POWV RNA and/or infectious POWV was detected in five pools of questing Ixodes scapularis larvae. Additionally, engorged female I. scapularis adults were collected from hunter-harvested white-tailed deer (Odocoileus virginianus) in a region with relatively high tick infection rates of POWV and allowed to oviposit under laboratory conditions. POWV RNA was detected in three female adult husks and one pool of larvae from a positive female. Infectious virus was isolated from all three RNA-positive females and the single positive larval pool. The detection of RNA and infectious virus in unfed questing larvae from the field and larvae from replete females collected from the primary tick host implicates vertical transmission as a potential mechanism for the maintenance of POWV in I. scapularis in nature, and elucidates the potential epidemiological significance of larval ticks in the transmission of POWV to humans. Full article
(This article belongs to the Special Issue Tick-Borne Viruses: Transmission and Surveillance)
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19 pages, 327 KiB  
Review
Acalculous Cholecystitis in COVID-19 Patients: A Narrative Review
by Evanthia Thomaidou, Eleni Karlafti, Matthaios Didagelos, Kalliopi Megari, Eleni Argiriadou, Karolina Akinosoglou, Daniel Paramythiotis and Christos Savopoulos
Viruses 2024, 16(3), 455; https://doi.org/10.3390/v16030455 - 15 Mar 2024
Viewed by 759
Abstract
Acute acalculous cholecystitis (AAC) represents cholecystitis without gallstones, occurring in approximately 5–10% of all cases of acute cholecystitis in adults. Several risk factors have been recognized, while infectious diseases can be a cause of cholecystitis in otherwise healthy people. Coronavirus disease 2019 (COVID-19) [...] Read more.
Acute acalculous cholecystitis (AAC) represents cholecystitis without gallstones, occurring in approximately 5–10% of all cases of acute cholecystitis in adults. Several risk factors have been recognized, while infectious diseases can be a cause of cholecystitis in otherwise healthy people. Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has spread worldwide, leading to an unprecedented pandemic. The virus enters cells through the binding of the spike protein to angiotensin-converting enzyme 2 (ACE2) receptors expressed in many human tissues, including the epithelial cells of the gastrointestinal (GI) tract, and this explains the symptoms emanating from the digestive system. Acute cholecystitis has been reported in patients with COVID-19. The purpose of this review is to provide a detailed analysis of the current literature on the pathogenesis, diagnosis, management, and outcomes of AAC in patients with COVID-19. Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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