Viruses

22 pages, 1012 KB

Open AccessReview

Evolving Threats: Adaptive Mechanisms of Monkeypox Virus (MPXV) in the 2022 Global Outbreak and Their Implications for Vaccine Strategies

by Yuanwen Wang, Meimei Hai, Zijie Guo, Junbo Wang, Yong Li and Weifeng Gao

Viruses 2025, 17(9), 1194; https://doi.org/10.3390/v17091194 (registering DOI) - 30 Aug 2025

Abstract

Monkeypox virus (MPXV) experienced an unprecedented global outbreak in 2022, characterized by a significant departure from historical patterns: a rapid spread of the epidemic to more than 110 non-traditional endemic countries, with more than 90,000 confirmed cases; a fundamental shift in the mode [...] Read more.

Monkeypox virus (MPXV) experienced an unprecedented global outbreak in 2022, characterized by a significant departure from historical patterns: a rapid spread of the epidemic to more than 110 non-traditional endemic countries, with more than 90,000 confirmed cases; a fundamental shift in the mode of transmission, with human-to-human transmission (especially among men who have sex with men (MSM)) becoming the dominant route (95.2%); and genetic sequencing revealing a key adaptive mutation in a novel evolutionary branch (Clade IIb) that triggered the outbreak. These features highlight the significant evolution of MPXV in terms of host adaptation, transmission efficiency, and immune escape ability. The aim of this paper is to provide insights into the viral adaptive evolutionary mechanisms driving this global outbreak, with a particular focus on the role of immune escape (e.g., novel mechanisms of M2 proteins targeting the T cell co-stimulatory pathway) in enhancing viral transmission and pathogenicity. At the same time, we systematically evaluate the cross-protective efficacy and limitations of existing vaccines (ACAM2000, JYNNEOS, and LC16), as well as recent advances in novel vaccine platforms, especially mRNA vaccines, in inducing superior immune responses. The study further reveals the constraints to outbreak control posed by grossly unequal global vaccine distribution (e.g., less than 10% coverage in high-burden regions such as Africa) and explores the urgency of optimizing stratified vaccination strategies and facilitating technology transfer to promote equitable access. The core of this paper is to elucidate the dynamic game between viral evolution and prevention and control strategies (especially vaccines). The key to addressing the long-term epidemiological challenges of MPXV in the future lies in continuously strengthening global surveillance of viral evolution (early warning of highly transmissible/pathogenic variants), accelerating the development of next-generation vaccines based on new mechanisms and platforms (e.g., multivalent mRNAs), and resolving the vaccine accessibility gap through global collaboration to build an integrated defense system of “Surveillance, Research and Development, and Equitable Vaccination,” through global collaboration to address the vaccine accessibility gap. Full article

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

► Show Figures

Figure 1

17 pages, 2037 KB

Open AccessArticle

First Detection and Identification of Southern Tomato Virus Infecting Tomatoes in Oklahoma with Complete Genome Characterization and Insights into Global Genetic Diversity

by Salil Jindal and Akhtar Ali

Viruses 2025, 17(9), 1193; https://doi.org/10.3390/v17091193 (registering DOI) - 30 Aug 2025

Abstract

Southern tomato virus (STV) or Amalgavirus lycopersici is a persistent virus impacting tomato crops globally. This study identified new STV isolates from Oklahoma and analyzed their evolutionary relationship to global STV isolates. Phylogenetic analyses (complete genomes or individual genes) grouped STV isolates into [...] Read more.

Southern tomato virus (STV) or Amalgavirus lycopersici is a persistent virus impacting tomato crops globally. This study identified new STV isolates from Oklahoma and analyzed their evolutionary relationship to global STV isolates. Phylogenetic analyses (complete genomes or individual genes) grouped STV isolates into two distinct clades, independent of geographic origin or host. Notably, Oklahoma isolates formed a separate cluster from previously reported isolates in the United States of America (USA). Coalescent analysis suggested the most recent common ancestor of STV fusion protein emerged around 135 years ago. Genetic diversity among STV isolates was low, with slightly more variability in the RNA-dependent RNA polymerase (RdRp) gene than the p42 gene. Both genes showed strong purifying selection. No recombination events were detected across complete genomes. Structure analysis revealed that the p42 protein, particularly its C-terminal region, displayed higher disorder, indicating a possible role in host interactions and viral adaptability. These findings deepen our understanding of STV’s evolution and highlight the need for ongoing surveillance and broader genomic sampling. Full article

(This article belongs to the Special Issue Plant Viral Pathogens: Innovations in Detection, Genetic Diversity, and Evolutionary Dynamics)

► Show Figures

Figure 1

23 pages, 323 KB

Open AccessReview

The Use of Nonhuman Primate Models for Advancing HIV PrEP

by Elena Bekerman and Christian Callebaut

Viruses 2025, 17(9), 1192; https://doi.org/10.3390/v17091192 (registering DOI) - 30 Aug 2025

Abstract

The global fight against HIV/AIDS has been significantly bolstered by the development and implementation of pre-exposure prophylaxis (PrEP), yet innovation in PrEP interventions, improved adherence and greater access are still needed to maximize its benefit. Nonhuman primate (NHP) infection with simian immunodeficiency virus [...] Read more.

The global fight against HIV/AIDS has been significantly bolstered by the development and implementation of pre-exposure prophylaxis (PrEP), yet innovation in PrEP interventions, improved adherence and greater access are still needed to maximize its benefit. Nonhuman primate (NHP) infection with simian immunodeficiency virus (SIV) has served as an instrumental animal model in advancing HIV PrEP research. This review comprehensively examines the utility of NHP models in evaluating the efficacy, pharmacokinetics, and safety of diverse PrEP strategies, including oral, injectable, implantable, and topical formulations. It discusses the development of diverse challenge models that simulate human transmission routes and the advantages of NHPs in enabling controlled and mechanistically informative studies. It also highlights the successful translation of pivotal NHP studies evaluating tenofovir-based regimens as well the long-acting agents, cabotegravir and lenacapavir, into the clinical settings, emphasizing the consistently high predictive power of the NHP models for the HIV PrEP clinical efficacy. Finally, it underscores the importance of species-specific pharmacologic considerations and the value of NHP data in informing clinical trial design. As the global community strives to end the HIV epidemic as a public health threat in the absence of an efficacious prophylactic vaccine, NHP models make a critical contribution in the development of next-generation HIV prevention tools. Full article

(This article belongs to the Special Issue Simian Immunodeficiency Virus Models of HIV/AIDS in Nonhuman Primates, 2nd Edition)

19 pages, 2263 KB

Open AccessArticle

T-Cell Epitope-Based SARS-CoV-2 DNA Vaccine Encoding an Antigen Fused with Type 1 Herpes Simplex Virus Glycoprotein D (gD)

by Luana Raposo de Melo Moraes Aps, Aléxia Adrianne Venceslau-Carvalho, Carla Longo de Freitas, Bruna Felício Milazzotto Maldonado Porchia, Mariângela de Oliveira Silva, Lennon Ramos Pereira, Natiely Silva Sales, Guilherme Formoso Pelegrin, Ethiane Segabinazi, Karine Bitencourt Rodrigues, Jamile Ramos da Silva, Bianca da Silva Almeida, Jéssica Pires Farias, Maria Fernanda Castro-Amarante, Paola Marcella Camargo Minoprio, Luís Carlos de Souza Ferreira and Rúbens Prince dos Santos Alves

Viruses 2025, 17(9), 1191; https://doi.org/10.3390/v17091191 (registering DOI) - 30 Aug 2025

Abstract

Authorized SARS-CoV-2 vaccines elicit both antibody and T-cell responses; however, benchmark correlates and update decisions have largely emphasized neutralizing antibodies. Motivated by the complementary role of cellular immunity, we designed a prototype polyepitope DNA vaccine encoding conserved human and mouse T-cell epitopes from [...] Read more.

Authorized SARS-CoV-2 vaccines elicit both antibody and T-cell responses; however, benchmark correlates and update decisions have largely emphasized neutralizing antibodies. Motivated by the complementary role of cellular immunity, we designed a prototype polyepitope DNA vaccine encoding conserved human and mouse T-cell epitopes from non-structural proteins of the original strain SARS-CoV-2 lineage. Epitope selection was guided by in silico predictions for common HLA class I alleles in the Brazilian population and the mouse H-2Kb haplotype. To enhance immunogenicity, the polyepitope sequences were fused to glycoprotein D (gD) from Herpes Simplex Virus 1 (HSV-1), an immune activator of dendritic cells (DCs), leading to enhanced activation of antigen-specific T-cell responses. Mice were immunized with two doses of the electroporated DNA vaccine encoding the gD-fused polyepitope, which induced robust interferon-gamma– and tumor necrosis factor-alpha–producing T cell responses compared to control mice. In addition, K18-hACE2 transgenic mice showed protection against intranasal challenge with the original SARS-CoV-2 strain, with reduced clinical symptoms, less weight loss, and decreased viral burden in both lung and brain tissues. The results experimentally confirm the protective role of T cells in vaccine-induced protection against SARS-CoV-2 and open perspectives for the development of universal anti-coronavirus vaccines. Full article

(This article belongs to the Special Issue SARS-CoV-2, COVID-19 Pathologies, Long COVID, and Anti-COVID Vaccines)

► Show Figures

Figure 1

17 pages, 1464 KB

Open AccessArticle

Use of the Slow-Delivery Platform, VacSIM, Shapes the Host Immune Response to Increase Protection Against Influenza Infection

by Anna L. McCormick, Ted M. Ross, Donald A. Harn and Jarrod J. Mousa

Viruses 2025, 17(9), 1190; https://doi.org/10.3390/v17091190 (registering DOI) - 30 Aug 2025

Abstract

Influenza virus is a leading cause of global morbidity and mortality due to acute lower respiratory infection, even with the widespread use of multiple licensed influenza vaccines. However, antigenic drift during influenza replication can cause vaccine-induced antibodies to poorly neutralize influenza virus, thereby [...] Read more.

Influenza virus is a leading cause of global morbidity and mortality due to acute lower respiratory infection, even with the widespread use of multiple licensed influenza vaccines. However, antigenic drift during influenza replication can cause vaccine-induced antibodies to poorly neutralize influenza virus, thereby reducing vaccine effectiveness. To help overcome this problem, we leveraged a hydrogel platform with influenza hemagglutinin (HA) protein to induce prolonged antigen exposure. The hydrogel platform, Vaccine Self-Assembling Immune Matrix (VacSIM^®), in combination with recombinant influenza H1 or H3 HA protein antigens, increased antigen-specific antibody titers in vaccinated mice, which led to decreased disease severity after H1N1 infection for H1 HA-vaccinated mice and decreased lung viral titers after H3N2 challenge for H3 HA-vaccinated mice. Sera collected from mice immunized with VacSIM and HA also showed broader HAI activity, increasing by 1–3 log against a panel of influenza viruses. These results were consistent with the use of cocktail immunization, containing both an H1 and H3 HA, where mice immunized with VacSIM had an increase in antigen-specific antibody titers and decreased disease severity and lung viral titers against H1N1 and H3N2 influenza challenges, respectively. Finally, it was determined that a single immunization with VacSIM and H1 HA could provide protection against lethal H1N1 challenge compared to a group without VacSIM. In summary, we demonstrate that use of the slow-release platform VacSIM can improve the host immune response to vaccination and increase protection against influenza infection. Full article

(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)

► Show Figures

Figure 1

17 pages, 1286 KB

Open AccessArticle

Molecular Epidemiology of SARS-CoV-2 Detected from Different Areas of the Kandy District of Sri Lanka from November 2020–March 2022

by Bushran N. Iqbal, Sibra R. M. Shihab, Tao Zhang, Aadhil Ahamed, Shiyamalee Arunasalam, Samanthika Jagoda, Leo L. M. Poon, Malik Peiris and Faseeha Noordeen

Viruses 2025, 17(9), 1189; https://doi.org/10.3390/v17091189 - 29 Aug 2025

Abstract

A comprehensive analysis of the molecular epidemiology of SARS-CoV-2 in the Kandy District of Sri Lanka from November 2020 to March 2022 was conducted to address the limited genomic surveillance data available across the country. The study investigated the circulating SARS-CoV-2 lineages, their [...] Read more.

A comprehensive analysis of the molecular epidemiology of SARS-CoV-2 in the Kandy District of Sri Lanka from November 2020 to March 2022 was conducted to address the limited genomic surveillance data available across the country. The study investigated the circulating SARS-CoV-2 lineages, their temporal dynamics, and the associated mutational profiles in the study area. A total of 280 SARS-CoV-2-positive samples were selected, and 252 complete genomes were successfully sequenced using Oxford Nanopore Technology. Lineage classification was performed using the EPI2ME tool, while phylogenetic relationships were inferred through maximum likelihood and time-scaled phylogenetic trees using IQ-TREE2 and BEAST, respectively. Amino acid substitutions were analyzed to understand lineage-specific mutation patterns. Fifteen SARS-CoV-2 lineages were identified, and of those B.1.411 (36%) was the most prevalent, followed by Q.8 (21%), AY.28 (9.5%), and the Delta and Omicron variants. The lineage distribution showed a temporal shift from B.1.411 to Alpha, Delta, and finally the Omicron, mirroring the global trends. Time to the most recent common ancestor analyses provided estimates for the introduction of major variants, while mutation analysis revealed the widespread occurrence of D614G in the spike protein and lineage-specific mutations across structural, non-structural, and accessory proteins.Detection of the Epsilon variant (absent in other national-level studies) in November 2020, highlighted the regional heterogeneity viral spread. This study emphasizes the importance of localized genomic surveillance to capture the true diversity and evolution of SARS-CoV-2, to facilitate containment strategies in resource-limited settings. Full article

(This article belongs to the Section Coronaviruses)

20 pages, 7223 KB

Open AccessArticle

Application of Bovine Nasal Epithelial Cells as an In Vitro Model for Studying Viral Infection in the Upper Respiratory Tract

by Malte Pitters, Henrik Fritsch, Ang Su, Klaus Jung and Paul Becher

Viruses 2025, 17(9), 1188; https://doi.org/10.3390/v17091188 - 29 Aug 2025

Abstract

Bovine respiratory disease complex (BRDC) is a multifactorial and globally prevalent condition involving a combination of viral and bacterial pathogens, as well as environmental stressors. Viral agents often initiate infections in the upper respiratory tract (URT), predisposing animals to secondary bacterial infections and [...] Read more.

Bovine respiratory disease complex (BRDC) is a multifactorial and globally prevalent condition involving a combination of viral and bacterial pathogens, as well as environmental stressors. Viral agents often initiate infections in the upper respiratory tract (URT), predisposing animals to secondary bacterial infections and severe clinical manifestations. Among the key viral contributors to BRDC are bovine viral diarrhea virus (BVDV) and bovine herpesvirus 1 (BHV-1). In this study, submerged liquid cultures of undifferentiated bovine nasal epithelial cells (BNECs) were employed to investigate mono- and co-infections with BVDV and BHV-1. Epithelial barrier integrity was assessed to evaluate the cytopathic effects of BHV-1, while viral replication and release were quantified. Both viruses demonstrated polarized release, and BHV-1 infection exhibited a pronounced cytopathic effect. Notably, a preceding BVDV infection did not alter the progression or outcome of BHV-1 infection in this in vitro model. These findings suggest that primary BNEC cultures represent a valuable and physiologically relevant tool for studying viral dynamics and interactions associated with BRDC. Full article

(This article belongs to the Special Issue Bovine Viral Diarrhea Viruses and Other Pestiviruses)

17 pages, 639 KB

Open AccessReview

Gastrointestinal Infiltration in Influenza Virus Infection: Mechanisms and Clinical Insights

by Aakriti Dua, Bhavna Trehan, Shymaa E. Bilasy, Catherine Yang and Ahmed ElShamy

Viruses 2025, 17(9), 1187; https://doi.org/10.3390/v17091187 - 29 Aug 2025

Abstract

Background: Influenza, a primarily respiratory illness, frequently manifests with gastrointestinal (GI) symptoms including nausea, vomiting, diarrhea, and abdominal pain. In this review, we analyze mechanisms describing GI infiltration and subsequent involvement of the GI system during influenza infection. Direct mechanisms involve the [...] Read more.

Background: Influenza, a primarily respiratory illness, frequently manifests with gastrointestinal (GI) symptoms including nausea, vomiting, diarrhea, and abdominal pain. In this review, we analyze mechanisms describing GI infiltration and subsequent involvement of the GI system during influenza infection. Direct mechanisms involve the presence of viral particles in the GI tract and binding to sialic acid receptor, α2,3 and α2,6 linkages. The influenza virus may gain access to gut tissue via swallowing of respiratory secretions, hematogenous spread, or lymphocytic migration via the lung–gut axis. Indirect mechanisms involve immune system dysregulation via cytokine, interferon, and leukotriene flux, upregulation of consequential apoptotic pathways, or gut microbiome dysbiosis. Together, they promote secondary GI opportunistic infections. These findings improve our knowledge of GI infiltration during influenza infection which may aid in effective clinical diagnosis and treatment, ultimately improving patient outcomes. Full article

(This article belongs to the Special Issue Evolutionary Challenges of RNA Viruses: Insights from SARS-CoV-2 Variants and Emerging Respiratory Diseases)

► Show Figures

Figure 1

23 pages, 1289 KB

Open AccessArticle

Development and Clinical Validation of a Skin Test for In Vivo Assessment of SARS-CoV-2 Specific T-Cell Immunity

by Tikhon V. Savin, Vladimir V. Kopat, Elena D. Danilenko, Alexey A. Churin, Anzhelika M. Milichkina, Edward S. Ramsay, Ilya V. Dukhovlinov, Andrey S. Simbirtsev and Areg A. Totolian

Viruses 2025, 17(9), 1186; https://doi.org/10.3390/v17091186 - 29 Aug 2025

Abstract

A novel skin test for an in vivo assessment of SARS-CoV-2-specific T-cell immunity was developed using CoronaDermPS, a multiepitope recombinant polypeptide encompassing MHC II–binding CD4+ T-cell epitopes of the SARS-CoV-2 structural proteins (S, E, M) and full length nucleocapsid (N). In silico epitope [...] Read more.

A novel skin test for an in vivo assessment of SARS-CoV-2-specific T-cell immunity was developed using CoronaDermPS, a multiepitope recombinant polypeptide encompassing MHC II–binding CD4+ T-cell epitopes of the SARS-CoV-2 structural proteins (S, E, M) and full length nucleocapsid (N). In silico epitope prediction and modeling guided antigen design, which was expressed in Escherichia coli, was purified (>95% purity) and formulated for intradermal administration. Preclinical evaluation in guinea pigs, mice, and rhesus macaques demonstrated a robust delayed type hypersensitivity (DTH) response at optimal doses (10–75 µg), with no acute or chronic toxicity, mutagenicity, or adverse effects on reproductive organs. An integrated clinical analysis included 374 volunteers stratified by vaccination status (EpiVacCorona, Gam-COVID-Vac, CoviVac) prior to COVID-19 infection (Wuhan/Alpha, Delta, Omicron variants), and SARS-CoV-2–naïve controls. Safety assessments across phase I–II trials recorded 477 adverse events, of which >88% were mild and self-limiting; no severe or anaphylactic reactions occurred. DTH responses were measured at 24 h, 72 h, and 144 h post-injection by papule and hyperemia measurements. Overall, 282/374 participants (75.4%) exhibited a positive skin test. Receiver operating characteristic analysis yielded an overall AUC of 0.825 (95% CI: 0.726–0.924), sensitivity 79.5% (95% CI: 75.1–83.3%), and specificity 85.5% (95% CI: 81.8–88.7%), with comparable diagnostic accuracy across vaccine, and variant subgroups (AUC range 0.782–0.870). CoronaDerm-PS–based skin testing offers a simple, reproducible, and low-cost method for qualitative evaluation of T-cell–mediated immunity to SARS-CoV-2, independent of specialized laboratory equipment (Eurasian Patent No. 047119). Its high safety profile and consistent performance across diverse cohorts support its utility for mass screening and monitoring of cellular immune protection following infection or vaccination. Full article

(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)

► Show Figures

Figure 1

15 pages, 1263 KB

Open AccessArticle

Connecting the Evolution and Spread of Turkey Reovirus Across the United States: A Genomic Perspective

by Nakarin Pamornchainavakul, Jonathan T. Vannatta, Vikash K. Singh, Robert Porter, Sagar M. Goyal, Sunil K. Mor and Kimberly VanderWaal

Viruses 2025, 17(9), 1185; https://doi.org/10.3390/v17091185 - 29 Aug 2025

Abstract

A major cause of lameness in turkeys is reoviral arthritis, driven by turkey reovirus (TRV) infection. In the U.S., TRV was first isolated in the 1980s but re-emerged as a significant pathogen causing arthritis in 2011. Since then, TRV outbreaks have spread nationwide [...] Read more.

A major cause of lameness in turkeys is reoviral arthritis, driven by turkey reovirus (TRV) infection. In the U.S., TRV was first isolated in the 1980s but re-emerged as a significant pathogen causing arthritis in 2011. Since then, TRV outbreaks have spread nationwide across turkey-producing regions and have occasionally resulted in hepatitis-associated pathotypes. The absence of a consistently effective commercial vaccine continues to hinder disease control efforts. To better understand TRV’s evolutionary trajectory and transmission dynamics, we analyzed 211 complete TRV genome sequences collected across the U.S. from 2007 to 2021. Bayesian time-scaled phylogenetic and phylogeographic analyses were conducted for all ten genome segments to estimate gene flow among geographic regions, client groups, and pathotypes. The results reconstructed a coherent, decades-long history of TRV evolution, which revealed segment-specific differences in the evolutionary rates—particularly in S1c (σC protein coding region of S1) and M2—suggesting reassortment with other avian reoviruses during the 2011 emergence. Nationwide spread patterns indicated dominant transmission routes from the Eastern U.S. to Minnesota and from breeder to smallholder flocks, likely driven by inter-regional animal or feed movement via the multi-stage turkey production cycle. Pathotype transitions were more frequently observed from arthritis-associated strains to those causing hepatitis or cardiac lesions. These findings provide crucial insights to support national TRV control strategies and long-term monitoring by industry stakeholders. Full article

(This article belongs to the Special Issue Avian Reovirus)

15 pages, 1229 KB

Open AccessArticle

Seroprevalence of Neutralizing Antibodies in Healthy Adults, in Mexico, Against Human and Simian Adenovirus Types

by Raúl E. López, Margarita Valdés Alemán, Jesús M. Torres-Flores, Yordanis Pérez-Llano, David Alejandro Cabrera Gaytán, Clara Esperanza Santacruz Tinoco, Julio Elias Alvarado Yaah, Yu Mei Anguiano Hernández, Bernardo Martínez Miguel, José Esteban Muñoz Medina, Nancy Sandoval Gutiérrez, Ilse Ramos Lagunes, José Antonio Arroyo Pérez and Ramón A. González

Viruses 2025, 17(9), 1184; https://doi.org/10.3390/v17091184 - 29 Aug 2025

Abstract

Replication-defective adenoviruses are widely used as vectors for vaccines, but their efficacy may be compromised by the prevalence of pre-existing neutralizing antibodies from natural infections or prior vaccination with adenovirus-based vaccines. To overcome these limitations, less common human adenovirus (HAdV) types and simian [...] Read more.

Replication-defective adenoviruses are widely used as vectors for vaccines, but their efficacy may be compromised by the prevalence of pre-existing neutralizing antibodies from natural infections or prior vaccination with adenovirus-based vaccines. To overcome these limitations, less common human adenovirus (HAdV) types and simian adenoviruses (SAdV) have been explored as alternative vectors to the widely prevalent HAdV-C5. Despite their importance, there is limited information on the epidemiology of adenovirus immunity in many countries and geographical regions, including Mexico. In this study, we analyzed 2488 serum samples from healthy adults across all 32 states of Mexico to assess the prevalence of both total and neutralizing antibodies against various HAdV types from species A-F, and three related SAdVs. Our findings indicate a high prevalence of neutralizing antibodies against HAdV-C5 and HAdV-C6, with significant cross-reactivity observed among related adenoviruses. Notably, HAdV-D26 exhibited a lower prevalence of neutralizing antibodies, suggesting its potential suitability as a vector for vaccine development in populations with high pre-existing immunity to more common HAdV types. These results provide critical insights for optimizing adenovirus-based vaccine strategies in Mexico. Full article

(This article belongs to the Special Issue Epidemiology, Pathogenesis and Immunity of Adenovirus)

► Show Figures

Figure 1

13 pages, 1635 KB

Open AccessArticle

Molecular Characterization of Emerging and Uncommon Enteroviruses C104, C105, and C109 in Respiratory Samples from Maryland, USA, 2018–2024

by Amary Fall, Ting X. Zhuang, Alaina Dodge, Omar Abdullah, Julie M. Norton, David Villafuerte, Andrew Pekosz, Eili Klein and Heba H. Mostafa

Viruses 2025, 17(9), 1183; https://doi.org/10.3390/v17091183 - 29 Aug 2025

Abstract

Background: While enteroviruses (EVs) are recognized causes of diverse illnesses, little is known about the epidemiology and molecular characteristics of uncommon enterovirus C (EV-C) types, including EV-C104, EV-C105, and EV-C109. Methods: We conducted genomic surveillance of EVs at the Johns Hopkins [...] Read more.

Background: While enteroviruses (EVs) are recognized causes of diverse illnesses, little is known about the epidemiology and molecular characteristics of uncommon enterovirus C (EV-C) types, including EV-C104, EV-C105, and EV-C109. Methods: We conducted genomic surveillance of EVs at the Johns Hopkins Health System between 2018 and 2024 (a total of 3715 samples), identifying EV-C104, EV-C105, and EV-C109 in respiratory samples. VP4-VP2 and whole-genome sequencing were used to assess genetic diversity and intra-host evolution. Results: Five EV-C105 infections were identified primarily in pediatric patients, presenting with a range of clinical features including fever, gastrointestinal symptoms, and cerebellitis. Prolonged EV-C104 and EV-C109 infections were identified in two immunocompromised adults. EV-C104 persisted for over five months and showed evidence of viral genomic changes (intra-host evolution). EV-C109 was detected over a four-month period. Phylogenetic analysis revealed a novel EV-C105 clade (C3) closely related to recent USA strains. EV-C104 genomes aligned with genotype B sequences from the USA and Europe, while EV-C109 sequences were similar to 2014–2015 strains from the Netherlands. Conclusions: These findings highlight the emergence, persistence, and genetic evolution of uncommon EV-C types in Maryland, especially among immunocompromised hosts, emphasizing the importance of continued genomic surveillance and clinical correlations. Full article

(This article belongs to the Special Issue Enteric Viruses in Environment and Humans: Identification, Surveillance and Control)

► Show Figures

Figure 1

12 pages, 235 KB

Open AccessArticle

Predictive Factors for HBsAg Seroconversion Following Acute Hepatitis B Virus Infection: A Multicenter BUHASDER Study

by Ozge Caydasi, Derya Öztürk Engin, Ömer Karaşahin, Ayşe Batırel, Süleyman Dolu, Müge Toygar Deniz, Sıla Akhan, Kemalettin Özden, Selma Tosun, Burak Sarıkaya, Levent Görenek, Merve Çelik Aydoğdu, Eyüp Arslan, Fatma Yılmaz Karadağ, Serpil Erol, Semiha Çelik Ekinci, Ahmet Şahin, Müge Özgüler, Pınar Yürük Atasoy, Derya Seyman, Süleyman Yıldırım, Gözde Derviş Hakim, Tuba Damar Çakırca, Özlem Bayraktar Saral, Tuğba Sarı, Türkkan Öztürk Kaygusuz, Süleyman Günay and Şükran Köse Show full author list Hide full author list

Viruses 2025, 17(9), 1182; https://doi.org/10.3390/v17091182 - 29 Aug 2025

Abstract

Experience with the effect of antiviral therapy on HBsAg seroconversion in acute hepatitis B is limited. We aimed to evaluate the factors affecting HBsAg seroconversion in patients with acute hepatitis B (AHB) receiving antiviral treatment. We performed a retrospective and multicenter study involving [...] Read more.

Experience with the effect of antiviral therapy on HBsAg seroconversion in acute hepatitis B is limited. We aimed to evaluate the factors affecting HBsAg seroconversion in patients with acute hepatitis B (AHB) receiving antiviral treatment. We performed a retrospective and multicenter study involving 107 adult patients who received antiviral treatment for AHB between January 2018 and December 2024. The median age was 48 (min–max, 18–91) years, and 66.3% of the patients were male; 70 patients with 24-week follow-up (15 patients without HBsAg seroconversion versus 55 patients with HBsAg seroconversion) were compared based on HBsAg seroconversion status. Multivariate logistic regression analysis revealed that age was independently associated with HBsAg seroconversion (odds ratio = 0.926; 95% confidence interval (CI) 0.874 to 0.981; p = 0.009). A one-year increase in age was associated with a 0.926-fold decrease in HBsAg seroconversion. In conclusion, age was an independent predictor of HBsAg seroconversion following acute hepatitis B virus infection. Full article

(This article belongs to the Special Issue Virological and Immunological Factors Underlying HBV Functional Cure and HBV Reactivation)

23 pages, 4473 KB

Open AccessArticle

Unexpected Clinical and Laboratory Observations During and After 42-Day Versus 84-Day Treatment with Oral GS-441524 in Cats with Feline Infectious Peritonitis with Effusion

by Katharina Buchta, Anna-Maria Zuzzi-Krebitz, Michèle Bergmann, Roswitha Dorsch, Katharina Zwicklbauer, Kaspar Matiasek, Regina Hofmann-Lehmann, Marina L. Meli, Andrea M. Spiri, Yury Zablotski, Martin Alberer, Ulrich von Both and Katrin Hartmann

Viruses 2025, 17(9), 1181; https://doi.org/10.3390/v17091181 - 29 Aug 2025

Abstract

The nucleoside analogue GS-441524 is a common treatment for cats with feline infectious peritonitis (FIP). In a previous study, 40 cats with FIP with effusion were treated with 15 mg/kg GS-441524 orally once daily for either 42 days or 84 days, and a [...] Read more.

The nucleoside analogue GS-441524 is a common treatment for cats with feline infectious peritonitis (FIP). In a previous study, 40 cats with FIP with effusion were treated with 15 mg/kg GS-441524 orally once daily for either 42 days or 84 days, and a 42-day treatment was as effective as the earlier recommended 84-day treatment. The aim of the present study was to describe unexpected clinical and laboratory observations occurring during and after treatment (within one year) in these cats and to compare them regarding the different treatment durations. Thirty-eight cats recovered rapidly during treatment, two cats had to be euthanized, and one cat was lost to follow-up. During treatment, 25 cats developed diarrhea. Lymphocytosis occurred in 26/40 cats during treatment, eosinophilia in 25/40 during treatment, increased alanine aminotransferase activity in 22/40, alkaline phosphatase activity in 7/40, and symmetric dimethylarginine levels in 25/40. These unexpected observations occurred equally in both treatment duration groups, but statistically significantly more cats developed lymphocytosis and eosinophilia when treated for 84 days. Although most of the unexpected observations during GS-441524 treatment improved or disappeared after treatment termination, these conditions have to be monitored, and treatment should not be given for longer than necessary. Full article

(This article belongs to the Section Animal Viruses)

► Show Figures

Figure 1

29 pages, 704 KB

Open AccessReview

Interplay Between Bacterial Extracellular Vesicles and Phages: Receptors, Mechanisms, and Implications

by Angelika Bołoz, Valérie Lannoy, Tomasz Olszak, Zuzanna Drulis-Kawa and Daria Augustyniak

Viruses 2025, 17(9), 1180; https://doi.org/10.3390/v17091180 - 29 Aug 2025

Abstract

Bacteria and phages have coexisted for billions of years engaging in continuous evolutionary arms races that drive reciprocal adaptations and resistance mechanisms. Among the diverse antiviral strategies developed by bacteria, modification or masking phage receptors as well as their physical removal via extracellular [...] Read more.

Bacteria and phages have coexisted for billions of years engaging in continuous evolutionary arms races that drive reciprocal adaptations and resistance mechanisms. Among the diverse antiviral strategies developed by bacteria, modification or masking phage receptors as well as their physical removal via extracellular vesicles are the first line of defense. These vesicles play a pivotal role in bacterial survival by mitigating the effects of various environmental threats, including predation by bacteriophages. The secretion of extracellular vesicles represents a highly conserved evolutionary trait observed across all domains of life. Bacterial extracellular vesicles (BEVs) are generated by a wide variety of Gram (+), Gram (−), and atypical bacteria, occurring under both natural and stress conditions, including phage infection. This review addresses the multifaceted role of BEVs in modulating bacteria–phage interactions, considering the interplay from both bacterial and phage perspectives. We focus on the dual function of BEVs as both defensive agents that inhibit phage infection and as potential facilitators that may inadvertently enhance bacterial susceptibility to phages. Furthermore, we discuss how bacteriophages can influence BEV production, affecting both the quantity and molecular composition of vesicles. Finally, we provide an overview of the ecological relevance and efficacy of BEV–phage interplay across diverse environments and microbial ecosystems. Full article

(This article belongs to the Section Bacterial Viruses)

► Show Figures

Figure 1

13 pages, 1448 KB

Open AccessArticle

The Diagnostic Value of Signal-to-Cutoff Ratios in Architect and Alinity HIV Screening Assays: A 10-Year Experience in a Pandemic-Affected, Low-Prevalence Setting

by İmran Sağlık, Melda Payaslıoğlu, Hatice Ortaç and Hülya Ayma Rüzgar

Viruses 2025, 17(9), 1179; https://doi.org/10.3390/v17091179 - 29 Aug 2025

Abstract

Early and accurate diagnosis of HIV remains a cornerstone of public health strategies. This study aimed to evaluate the predictive value of signal-to-cutoff (S/CO) ratios from two fourth-generation HIV screening assays (Abbott Architect and Alinity) and to analyze diagnostic trends across pre-pandemic, pandemic, [...] Read more.

Early and accurate diagnosis of HIV remains a cornerstone of public health strategies. This study aimed to evaluate the predictive value of signal-to-cutoff (S/CO) ratios from two fourth-generation HIV screening assays (Abbott Architect and Alinity) and to analyze diagnostic trends across pre-pandemic, pandemic, and post-pandemic periods in a low-prevalence setting. We retrospectively analyzed 197,642 unique HIV screening tests conducted at Bursa Uludağ University Hospital from 2015 to 2024. Receiver operating characteristic (ROC) analysis was used to determine optimal S/CO thresholds for distinguishing true-positive results. Of the 197,642 samples screened, the overall HIV prevalence was 0.5%, with 196 cases (0.1%) confirmed as new diagnoses. The Architect assay showed an optimal S/CO threshold of ≥11.8 (sensitivity 98.3%, specificity 97.3%). The Alinity assay demonstrated 100% sensitivity and specificity at an S/CO threshold of ≥19.1. Although a temporary decline in test volume occurred in 2020, there was no statistically significant difference in confirmation rates across years. During the pandemic, newly diagnosed individuals were significantly older and had lower CD4 counts, indicating delayed diagnosis (p = 0.026 and 0.008, respectively). Men who have sex with men (MSM)-related transmission significantly increased post-pandemic (p = 0.032). S/CO ratio–guided interpretation enhances diagnostic accuracy and may reduce unnecessary confirmatory testing, especially in low-prevalence and resource-limited regions. Selecting the optimal threshold can help to ensure a timely diagnosis and optimize HIV screening algorithms. Full article

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

► Show Figures

Figure 1

46 pages, 2436 KB

Open AccessReview

Antiviral Strategies Targeting Enteroviruses: Current Advances and Future Directions

by Michelle Felicia Lee, Seng Kong Tham and Chit Laa Poh

Viruses 2025, 17(9), 1178; https://doi.org/10.3390/v17091178 - 28 Aug 2025

Abstract

Enteroviruses, a diverse genus within the Picornaviridae family, are responsible for a wide range of human infections, including hand, foot, and mouth disease, respiratory disease, aseptic meningitis, encephalitis, myocarditis, and acute flaccid paralysis. Despite their substantial global health burden and the frequent emergence [...] Read more.

Enteroviruses, a diverse genus within the Picornaviridae family, are responsible for a wide range of human infections, including hand, foot, and mouth disease, respiratory disease, aseptic meningitis, encephalitis, myocarditis, and acute flaccid paralysis. Despite their substantial global health burden and the frequent emergence of outbreaks, no specific antiviral therapies are currently approved for clinical use against non-polio enteroviruses. This review provides a comprehensive overview of the current landscape of antiviral strategies targeting enteroviruses, including direct-acting antivirals such as capsid binders, protease inhibitors, and viral RNA polymerase inhibitors. We also examine the potential of host-targeting agents that interfere with virus–host interactions essential for replication. Emerging strategies such as immunotherapeutic approaches, RNA interference, CRISPR-based antivirals, and peptide-based antivirals are also explored. Furthermore, we address key challenges, including viral diversity, drug resistance, and limitations in preclinical models. By highlighting recent advances and ongoing efforts in antiviral development, this review aims to guide future research and accelerate the discovery of effective therapies against enterovirus infections. Full article

(This article belongs to the Special Issue Picornavirus Evolution, Host Adaptation and Antiviral Strategies)

► Show Figures

Figure 1

15 pages, 3579 KB

Open AccessArticle

Pathogenicity of SARS-CoV-2 Omicron Subvariants JN.1, KP.2, and EG.5.1 in K18-hACE2 Transgenic Mice

by Lila D. Patterson, Amany Elsharkawy, Hamid Reza Jahantigh, Zainab Nabi, Shannon Stone and Mukesh Kumar

Viruses 2025, 17(9), 1177; https://doi.org/10.3390/v17091177 - 28 Aug 2025

Abstract

The emergence of the SARS-CoV-2 JN.1 lineage in late 2023 marked a major shift in viral evolution. By January 2024, it had displaced XBB variants to become the dominant strain worldwide. JN.1 and its descendants are antigenically distinct from earlier Omicron subvariants, with [...] Read more.

The emergence of the SARS-CoV-2 JN.1 lineage in late 2023 marked a major shift in viral evolution. By January 2024, it had displaced XBB variants to become the dominant strain worldwide. JN.1 and its descendants are antigenically distinct from earlier Omicron subvariants, with approximately 30 additional spike mutations compared to XBB-derived viruses. The combination of these features alongside growing evidence of considerable immune evasion prompted the FDA to recommend that vaccine formulations be updated to target JN.1 rather than XBB.1.5. The continued dominance of JN.1-derived variants necessitates the characterization of viral infection in established animal models to inform vaccine efficacy and elucidate host–pathogen interactions driving disease outcomes. In this study, transgenic mice expressing human ACE2 were infected with SARS-CoV-2 subvariants JN.1, KP.2, and EG.5.1 to compare the pathogenicity of JN.1-lineage and XBB-lineage SARS-CoV-2 viruses. Infection with JN.1 and KP.2 resulted in attenuated disease, with animals exhibiting minimal clinical symptoms and no significant weight loss. In contrast, EG.5.1-infected mice exhibited rapid progression to severe clinical disease, substantial weight loss, and 100% mortality within 7 days of infection. All variants replicated effectively within the upper and lower respiratory tracts and caused significant lung pathology. Notably, EG.5.1 resulted in neuroinvasive infection with a significantly high viral burden in the brain. Additionally, EG.5.1 infection resulted in a significant increase in CD8⁺ T cell and CD11b⁺ CD11c⁺ dendritic cell populations in infected lungs. Full article

(This article belongs to the Special Issue Multiple Hosts of SARS-CoV-2, 3rd Edition)

► Show Figures

Figure 1

18 pages, 5170 KB

Open AccessArticle

APOBEC3B Promotes SARS-CoV-2 Through Activation of PKR/eIF2⍺ and AMPD2 Dysregulation

by Benjamin Fixman, Lavanya Manjunath, Philip Sell, Shanshan Wang, Tamara Margaryan, Connor Qiu, Hanjing Yang, Rémi Buisson and Xiaojiang S. Chen

Viruses 2025, 17(9), 1176; https://doi.org/10.3390/v17091176 - 28 Aug 2025

Abstract

APOBEC3B (A3B) has been implicated in host–virus interactions, but its role in SARS-CoV-2 infection is unclear. Here, we demonstrate that A3B is overexpressed in bronchoalveolar lavage fluid (BALF) cells from severe COVID-19 patients compared to those with mild disease. A3B knockdown in Caco-2 [...] Read more.

APOBEC3B (A3B) has been implicated in host–virus interactions, but its role in SARS-CoV-2 infection is unclear. Here, we demonstrate that A3B is overexpressed in bronchoalveolar lavage fluid (BALF) cells from severe COVID-19 patients compared to those with mild disease. A3B knockdown in Caco-2 cells significantly reduces SARS-CoV-2 infectivity, likely through attenuation of the PKR-mediated integrated stress response, a pathway proposed to promote SARS-CoV-2. Single-cell RNA sequencing (scRNA-seq) data suggest that BALF cells from severe COVID-19 patients exhibit a repressed state for cellular translation, potentially mediated by eIF2α phosphorylation. However, in A549-ACE2 cells, SARS-CoV-2 does not activate PKR, but A3B knockdown still reduces SARS-CoV-2 infectivity, suggesting an alternative mechanism of action in different cellular contexts. To further investigate A3B’s role in severe COVID-19, we employed Geneformer, a transformer-based machine learning model, which predicted that A3B knockout would perturb AMPD2 (adenosine monophosphate deaminase 2), a key enzyme in purine metabolism and immune regulation. We validated this prediction using bulk RNA-seq and clinical scRNA-seq data, confirming that AMPD2 expression is downregulated in severe COVID-19 but restored upon A3B knockdown. Together, these findings suggest that A3B plays a proviral role in SARS-CoV-2 infection by modulating translational control and immune regulatory networks, warranting further studies to elucidate the underlying mechanistic details. Full article

(This article belongs to the Special Issue Host-Mediated Viral Mutations: APOBECs, ADARs, and Beyond)

► Show Figures

Graphical abstract

Journal Description

Viruses

Latest Articles

Journal Menu

Journal Browser

Highly Accessed Articles

Latest Books

E-Mail Alert

News

Topics

Conferences

Special Issues

Topical Collections

Further Information

Guidelines

MDPI Initiatives

Follow MDPI