Viruses

9 pages, 608 KB

Open AccessBrief Report

“Big Events” and HIV Transmission Dynamics: Estimating Time Since HIV Infection from Deep Sequencing Data Among Sex Workers and Their Clients in Dnipro, Ukraine

by François Cholette, Nicole Herpai, Leigh M. McClarty, Olga Balakireva, Daryna Pavlova, Anna Lopatenko, Rupert Capiña, Paul Sandstrom, Michael Pickles, Evelyn Forget, Sharmistha Mishra, Marissa L. Becker and on behalf of the Dynamics Study Team

Viruses 2025, 17(8), 1148; https://doi.org/10.3390/v17081148 - 21 Aug 2025

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Abstract

Background: Major geopolitical events and structural shocks are thought to play a significant role in shaping HIV epidemics by influencing individual behaviours, reshaping social networks, and impacting HIV prevention and treatment programs. Here, we describe individual-level measures of estimated time since HIV infection [...] Read more.

Background: Major geopolitical events and structural shocks are thought to play a significant role in shaping HIV epidemics by influencing individual behaviours, reshaping social networks, and impacting HIV prevention and treatment programs. Here, we describe individual-level measures of estimated time since HIV infection (ETI) from viral next-generation sequencing data among female sex workers and their clients in relation to significant geopolitical events in Ukraine. Methods: The Dynamics Study is a cross-sectional integrated biological and behavioural survey conducted among female sex workers and their clients in Dnipro, Ukraine (December 2017 to March 2018). We were able to successfully sequence a portion of the HIV pol gene on dried blood spot specimens among n = 5/9 clients and n = 5/16 female sex workers who tested positive for HIV (total n = 10/25) using an in-house drug resistance genotyping assay. The “HIV EVO” Intrapatient HIV Evolution web-based tool was used to infer ETI from viral diversity. Results: The median ETIs for female sex workers and their clients were 5.4 years (IQR = 2.9, 6.6) and 6.5 years (IQR = 5.4, 10.8), respectively. Nearly all HIV acquisition events (n = 7/10; 70%) were estimated to have occurred between the Great Recession (2008–2009) and the War in Donbas (May 2014–February 2022). In general, ETI suggests that HIV acquisition occurred earlier among clients (2012 [IQR = 2007, 2013]) compared to sex workers (2013 [IQR = 2012, 2016]). Conclusion: Our findings suggest that most HIV acquisition in this small subset of female sex workers and clients living with HIV occurred during periods of economic decline. Molecular studies on timing of HIV acquisition against timing of major geopolitical events offer a novel way to contextualize how such events may shape transmission patterns. Full article

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

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14 pages, 632 KB

Open AccessArticle

Prevalence and Associated Factors for HPV in People Living with HIV: Are INSTIs Protective Against HPV-16? The GAIA Study

by Omar Hernández-López, Brenda Clara González-Contreras, Ana Luz Cano-Díaz, José Antonio Mata-Marín, Ericka Nelly Pompa-Mera, Javier Vicente Noyola-Gómez, Salma Triana-González, Paola Edith Padilla-Noguera, Alberto Chaparro-Sánchez, Sócrates Alberto García-Gutiérrez, Gustavo Barriga-Angulo and Jesús Enrique Gaytan-Martinez

Viruses 2025, 17(8), 1147; https://doi.org/10.3390/v17081147 - 21 Aug 2025

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Abstract

Human papillomavirus (HPV) significantly contributes to anogenital cancers, with elevated risks among people living with HIV (PWH), particularly men who have sex with men (MSM). This study assessed anal HPV prevalence and associated risk factors in PWH in Mexico, focusing on the role [...] Read more.

Human papillomavirus (HPV) significantly contributes to anogenital cancers, with elevated risks among people living with HIV (PWH), particularly men who have sex with men (MSM). This study assessed anal HPV prevalence and associated risk factors in PWH in Mexico, focusing on the role of antiretroviral therapy (ART). Methods: A cross-sectional study at an HIV clinic in Mexico City (October 2023–December 2024) enrolled 214 MSM with HIV. The participants completed a validated risk factor questionnaire and provided anal samples for real-time PCR testing of 28 HPV genotypes. Logistic regression analyzed associations between HPV infection, ART regimens, and clinical/behavioral factors. Results: HPV prevalence was 89.3%, with HPV-16 (20.1%) being the most common high-risk genotype. Integrase inhibitor (INSTI) use was inversely associated with HPV-16 infection (OR: 0.42; 95% CI: 0.21–0.83; p = 0.011), while protease inhibitor use increased HPV-16 (OR: 2.16; 95% CI: 1.09–4.29; p = 0.025) and HPV-6 risks. Higher CD4+ counts (≥500 cells/mm³) and undetectable HIV viral load (<40 copies/mL) were protective against multiple HPV genotypes. Lower education and smoking increased HPV risk. Conclusions: This first Mexican study in the ART and HPV vaccination era highlights high anal HPV prevalence in PWH and suggests that INSTI-based regimens may reduce HPV-16 risk, informing ART selection for HPV prevention. Full article

(This article belongs to the Special Issue Cascade of Care for HIV, Hepatitis and Sexually Transmitted Infections)

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14 pages, 1721 KB

Open AccessBrief Report

Serologic Evidence of Human Exposure to Bat-Borne Zoonotic Paramyxoviruses, Cambodia

by Neil Mittal, Spencer L. Sterling, Phireak Hip, Dolyce H. W. Low, Piseth Ly, Menghou Mao, Pidor Ouch, Adrian C. Paskey, Lianying Yan, Alan Hitch, Gavin J. D. Smith, Jeffery Hertz, Andrew G. Letizia, Ian H. Mendenhall and Eric D. Laing

Viruses 2025, 17(8), 1146; https://doi.org/10.3390/v17081146 - 21 Aug 2025

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Abstract

Fruit bats in the genus Pteropus are the natural reservoirs for zoonotic paramyxoviruses, notably henipaviruses and pararubulaviruses, which are found across Southeast Asia and Oceania. The genetic and antigenic diversity of viruses in both genera, and region specificity, are ill-defined, limiting health security [...] Read more.

Fruit bats in the genus Pteropus are the natural reservoirs for zoonotic paramyxoviruses, notably henipaviruses and pararubulaviruses, which are found across Southeast Asia and Oceania. The genetic and antigenic diversity of viruses in both genera, and region specificity, are ill-defined, limiting health security measures aimed at minimizing spillover. For example, Nipah virus has been isolated from bats in the Battambang province of western Cambodia, and surveys suggest bat foraging behaviors occur in close proximity to human settlements. However, there have been no historical cases of Nipah virus in Cambodia. Here, we use a multiplex microsphere immunoassay to identify cryptic human exposure to selected henipaviruses and pararubulaviruses in Cambodia. Convalescent human sera from persons presenting with acute respiratory illness were screened to detect the presence or absence of antibodies reactive with attachment glycoprotein antigens from Nipah virus, Hendra virus, Cedar virus, and Ghana virus, and a hemagglutinin-neuraminidase antigen from Menangle virus. In this sero-survey, we detected antibodies that were specifically reactive with Cedar virus and Menangle virus, including one serum sample that neutralized a recombinant Cedar virus. Additionally, we detected a pattern of cross-reactivity with Hendra virus, Cedar virus, and Ghana virus, suggesting previous infection by an antigenically-related henipavirus. We did not detect high antibody reactivity with the NiV glycoprotein. Future studies should expand serological surveillance for these transboundary pathogens, including genetic surveillance to aid in henipavirus discovery, and focused biosurveillance where interfaces with livestock and humans occur. Full article

(This article belongs to the Special Issue Emerging Zoonotic Paramyxoviruses)

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28 pages, 5717 KB

Open AccessReview

The Role of Myxoma Virus Immune Modulators and Host Range Factors in Pathogenesis and Species Leaping

by Junior A. Enow, Ana M. Lopes, Joana Abrantes, Pedro J. Esteves and Masmudur M. Rahman

Viruses 2025, 17(8), 1145; https://doi.org/10.3390/v17081145 - 21 Aug 2025

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Abstract

Myxoma virus (MYXV) is a leporipoxvirus that causes lethal disease in Leporids. Hares and rabbits belong to the Leporidae family and are believed to have had a common ancestor 12 million years ago. After seventy years of contact with European hares without causing [...] Read more.

Myxoma virus (MYXV) is a leporipoxvirus that causes lethal disease in Leporids. Hares and rabbits belong to the Leporidae family and are believed to have had a common ancestor 12 million years ago. After seventy years of contact with European hares without causing mortalities or disease manifestation, a recombinant MYXV infected Iberian hares (Lepus granatensis) causing high mortalities. Like all poxviruses, MYXV encodes a wealth of immune modulators required for successful virulence that also mediate host species jumping, for example, into hares. Here, we summarize the data of known MYXV immune modulators, their cellular functions, and their effects on European rabbits. Additionally, we suggest that the critical restrictions MYXV would encounter in colonizing a potentially new host species stem from their interactions with the host’s innate immune environment. Lastly, we synthesize our understanding of some poxvirus genome architectural features that might have facilitated the host species jump of MYXV into hares from rabbits. Full article

(This article belongs to the Collection Poxviruses)

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21 pages, 3804 KB

Open AccessArticle

Diversity of RNA Viruses and Circular Viroid-like Elements in Heterobasidion spp. in Near-Natural Forests of Bosnia and Herzegovina

by László Benedek Dálya, Ondřej Hejna, Marcos de la Peña, Zoran Stanivuković, Tomáš Kudláček and Leticia Botella

Viruses 2025, 17(8), 1144; https://doi.org/10.3390/v17081144 - 20 Aug 2025

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Abstract

Heterobasidion root rot fungi represent a major threat to conifer forest stands, and virocontrol (biocontrol) has been proposed as an alternative strategy of disease management in recent years. Here, we investigated the occurrence of RNA viruses and viroid-like genomes in Heterobasidion annosum sensu [...] Read more.

Heterobasidion root rot fungi represent a major threat to conifer forest stands, and virocontrol (biocontrol) has been proposed as an alternative strategy of disease management in recent years. Here, we investigated the occurrence of RNA viruses and viroid-like genomes in Heterobasidion annosum sensu lato in near-natural forests of Bosnia and Herzegovina (Dinaric Alps), a region previously unexplored in this regard. Seventeen H. annosum s.l. isolates were screened for virus presence by RNA Sequencing and bioinformatic analyses. In total, 32 distinct mycoviruses were discovered in the datasets, 26 of which were previously unknown. The detected viruses represent two dsRNA (Partitiviridae and Curvulaviridae), six linear ssRNA (Mitoviridae, Narnaviridae, Botourmiaviridae, Virgaviridae, Benyviridae, and Deltaflexiviridae) and three circular ssRNA (Dumbiviridae, Quambiviridae, and Trimbiviridae) virus families. In addition to the known circular ambiviruses with their hammerhead (HHRz) and hairpin (HPRz) ribozymes, two other smaller non-coding circular RNAs of ca. 910 bp each were identified encoding HHRz and deltavirus (DVRz) ribozymes in both polarities of their genomes. This study documents the first report of a putative viroid-like RNA agent in Heterobasidion, along with beny-like and deltaflexivirus-like viruses in Heterobasidion abietinum, and expands the known virosphere of Heterobasidion species in Southeastern European forests. Full article

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20 pages, 688 KB

Open AccessArticle

Cannabis Use Moderates Methamphetamine- and HIV-Related Inflammation: Evidence from Human Plasma Markers

by Jeffrey M. Rogers, Victoria O. Chentsova, Crystal X. Wang, Maria Cecilia Garibaldi Marcondes, Mariana Cherner, Ronald J. Ellis, Scott L. Letendre, Robert K. Heaton, Igor Grant and Jennifer E. Iudicello

Viruses 2025, 17(8), 1143; https://doi.org/10.3390/v17081143 - 20 Aug 2025

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Abstract

Background: Methamphetamine use, which is disproportionately prevalent among people with HIV, increases risk for cardio- and neurovascular pathology through persistent immune activation and inflammation. Preclinical studies indicate that cannabinoids may reduce markers of pro-inflammatory processes, but data from people with chronic inflammatory conditions [...] Read more.

Background: Methamphetamine use, which is disproportionately prevalent among people with HIV, increases risk for cardio- and neurovascular pathology through persistent immune activation and inflammation. Preclinical studies indicate that cannabinoids may reduce markers of pro-inflammatory processes, but data from people with chronic inflammatory conditions are limited. We examined potentially interacting associations of lifetime methamphetamine use disorder (MUD), recent cannabis use, and HIV with four plasma markers of immune and inflammatory functions. Method: Participants with HIV (PWH, n = 86) and without HIV (PWoH, n = 148) provided urine and blood samples and completed neuromedical, psychiatric, and substance use assessments. Generalized linear models examined main and conditional associations of lifetime MUD, past-month cannabis use, and HIV with plasma concentrations of CXCL10/IP-10, CCL2/MCP-1, ICAM-1, and VCAM-1. Results: PWH displayed higher CXCL10/IP-10 than PWoH. Past-month cannabis use was independently associated with lower CXCL10/IP-10 levels and conditionally lower CCL2/MCP-1, ICAM-1, and VCAM-1 levels among people with lifetime MUD, but only PWoH displayed cannabis-associated lower VCAM-1 levels. Conclusions: Human plasma sample evidence suggests that cannabis use is associated with lower levels of immune and inflammatory molecules in the context of MUD or HIV. Cannabinoid pathways may be worthwhile clinical targets for treating sequelae of chronic inflammatory conditions. Full article

(This article belongs to the Special Issue HIV and Drugs of Abuse, 4th Edition)

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14 pages, 2124 KB

Open AccessArticle

Determining the Importance of Carbohydrate-Based Structures in Murine Norovirus Binding to Commensal Bacteria

by Jasmine L. Madrigal, Joseph P. Sullivan, Feba Mathew, Melanie Lane and Melissa K. Jones

Viruses 2025, 17(8), 1142; https://doi.org/10.3390/v17081142 - 20 Aug 2025

Viewed by 479

Abstract

Norovirus–bacterial interactions influence viral replication and immune responses, yet the molecular details that mediate binding of these viruses to commensal bacteria are unknown. Studies with other enteric viruses have revealed that LPS and other lipid/carbohydrate structures facilitate virus–bacterial interactions, and it has also [...] Read more.

Norovirus–bacterial interactions influence viral replication and immune responses, yet the molecular details that mediate binding of these viruses to commensal bacteria are unknown. Studies with other enteric viruses have revealed that LPS and other lipid/carbohydrate structures facilitate virus–bacterial interactions, and it has also been shown that human noroviruses (HuNoVs) can interact with histo-blood group antigen (HBGA)-like compounds on the surface of bacterial cells. Based on these findings, this study hypothesized that carbohydrate-based compounds were the ligands that facilitated binding of both human and murine noroviruses (MNV) to bacteria. Using glycan microarrays, competitive inhibition assays, and a panel of bacterial mutants, the project assessed the influence of specific glycans on viral attachment to bacteria. Protein-based interactions were also examined. The results supported previous work which demonstrated that HuNoVs strongly bind HBGA-like glycans, while MNV displayed distinct binding to other glycans including aminoglycosides and fucosylated structures. Ultimately, this work demonstrates that HuNoVs have more limited binding requirements for bacterial attachment compared to MNV, and the MNV binding to bacteria may involve both specific structures as well as electrostatic interactions. Given the importance of commensal bacteria during viral infection, defining the molecular mechanisms that mediate virus–bacteria interactions is critical for understanding infection dynamics and may be useful in the development of disease therapeutics and novel technologies for viral detection from food and environmental sources. Full article

(This article belongs to the Special Issue Enteric Viruses, Bacteria, and the Virome in Health and Disease)

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19 pages, 4709 KB

Open AccessArticle

The Tetraspanin CD9 Facilitates SARS-CoV-2 Infection and Brings Together Different Host Proteins Involved in SARS-CoV-2 Attachment and Entry into Host Cells

by Vanessa Rivero, María Laura Saiz, Daniel Torralba, Carlos López-Larrea, Beatriz Suarez-Alvarez and Marta L. DeDiego

Viruses 2025, 17(8), 1141; https://doi.org/10.3390/v17081141 - 20 Aug 2025

Viewed by 525

Abstract

CD9 protein belongs to a family of proteins called tetraspanins, so named for their four-transmembrane-spanning architectures. These proteins are located in domains in the plasmatic membrane, called tetraspanin-enriched microdomains (TEMs). Several proteases and cellular receptors for virus entry cluster into TEMs, suggesting that [...] Read more.

CD9 protein belongs to a family of proteins called tetraspanins, so named for their four-transmembrane-spanning architectures. These proteins are located in domains in the plasmatic membrane, called tetraspanin-enriched microdomains (TEMs). Several proteases and cellular receptors for virus entry cluster into TEMs, suggesting that TEMs are preferred virus entry portals. Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein mediates virus attachment and entry into cells by binding to human angiotensin-converting enzyme 2 (ACE-2). In addition, the secretory, type-I membrane-bound SARS-CoV-2 S protein is synthesized as a precursor (proS) that undergoes posttranslational cleavages by host cell proteases, such as furin and TMPRSS2. Moreover, it has been shown that neuropilin-1 (NRP1), which is known to bind furin-cleaved substrates, potentiates SARS-CoV-2 infectivity. Our results indicate that CD9 facilitates SARS-CoV-2 infection. In addition, we show how knocking out CD9 leads to a decrease in the expression of NRP1, a protein that improves SARS-CoV-2 infection. Furthermore, we show that CD9 colocalizes with ACE-2, NRP1, furin, and TMPRSS2 at the plasma membrane; that the absence of CD9 decreases the expression of these proteins on the plasma membrane CD9-enriched microdomains, and that CD9 interacts with ACE2. In conclusion, our data suggest that CD9 facilitates SARS-CoV-2 infection and that CD9 brings together different host proteins involved in SARS-CoV-2 attachment and entry into host cells, such as ACE2, NRP1, furin, and TMPRSS2. Importantly, the fact that a blocking antibody targeting CD9 can effectively reduce SARS-CoV-2 titers highlights not only the mechanistic role of CD9 in viral entry but also offers translational potential, suggesting that tetraspanin-targeting antibodies could be developed as therapeutic agents against SARS-CoV-2 and possibly other coronaviruses, with meaningful implications for clinical intervention. Full article

(This article belongs to the Special Issue Coronaviruses Pathogenesis, Immunity, and Antivirals (2nd Edition))

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16 pages, 296 KB

Open AccessReview

Human Metapneumovirus: A Narrative Review on Emerging Strategies for Prevention and Treatment

by Nicola Principi, Valentina Fainardi and Susanna Esposito

Viruses 2025, 17(8), 1140; https://doi.org/10.3390/v17081140 - 20 Aug 2025

Viewed by 705

Abstract

Human metapneumovirus (HMPV) is a major cause of acute respiratory tract infections, particularly in infants, young children, older adults, and immunocompromised individuals. Since its discovery in 2001, the virus has been recognized for its significant clinical and socioeconomic impact. Despite extensive research, no [...] Read more.

Human metapneumovirus (HMPV) is a major cause of acute respiratory tract infections, particularly in infants, young children, older adults, and immunocompromised individuals. Since its discovery in 2001, the virus has been recognized for its significant clinical and socioeconomic impact. Despite extensive research, no licensed vaccines or antiviral therapies are currently available for HMPV. This review aims to synthesize current knowledge on HMPV prevention and treatment, and to highlight promising avenues for future interventions. Several monoclonal antibodies (mAbs) targeting conserved epitopes of the HMPV fusion (F) protein have shown strong neutralizing activity in vitro and in animal models, although none have reached clinical trials. Vaccine development, including subunit, live attenuated, vector-based, and mRNA platforms, is progressing, with some candidates showing promise in adult populations. However, data in children, especially seronegative infants, remain limited. Antiviral research has explored repurposed drugs such as ribavirin and probenecid, along with novel agents like fusion inhibitors and T-cell-based immunotherapies, though none are yet approved. The development of safe, effective interventions—especially multivalent approaches targeting multiple respiratory viruses—remains a high priority. Continued research is essential to bridge the gap between preclinical promise and clinical application and to reduce the burden of HMPV infection worldwide. Full article

(This article belongs to the Section General Virology)

22 pages, 3396 KB

Open AccessArticle

Novel Role of the Epstein-Barr Virus Encoded Deubiquitinating Enzyme (BPLF1) in mTOR-Mediated Cell Growth and Proliferation Pathways

by Rachel Mund, Sage L. Atkins, Anwen Cao, Aminatou Diallo and Christopher B. Whitehurst

Viruses 2025, 17(8), 1139; https://doi.org/10.3390/v17081139 - 20 Aug 2025

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Abstract

Epstein-Barr Virus (EBV) is a causative agent of infectious mononucleosis and is strongly associated with Burkitt lymphoma, Hodgkin lymphoma, and nasopharyngeal carcinoma. EBV encodes a deubiquitinating enzyme, BPLF1, which is important for infectious virus production, B-cell immortalization, and tumorigenesis. To elucidate BPLF1’s role, [...] Read more.

Epstein-Barr Virus (EBV) is a causative agent of infectious mononucleosis and is strongly associated with Burkitt lymphoma, Hodgkin lymphoma, and nasopharyngeal carcinoma. EBV encodes a deubiquitinating enzyme, BPLF1, which is important for infectious virus production, B-cell immortalization, and tumorigenesis. To elucidate BPLF1’s role, an affinity-based mass spectrometry screen was performed, which suggested that BPLF1 and mTOR interact. mTOR, a critical mediator within cellular signaling cascades and oncogenesis, exists in two distinct complexes: mTOR Complex 1 (mTORC1) and mTOR Complex 2 (mTORC2). Here, we show that BPLF1 has direct deubiquitinating (DUB) activity on mTOR, removing both K48- and K63-ubiquitin linkages. Additionally, WT BPLF1 decreased mTORC1 localization to the lysosome and decreased the phosphorylation of mTORC1 downstream effectors, 4E-BP1 and S6K1. BPLF1 also had DUB activity on Raptor and Rictor, which have both been shown to preferentially cause the formation of mTORC2 over mTORC1 when not ubiquitinated. Immunoprecipitation of mTOR shows decreased mTORC1 formation in the presence of WT BPLF1. Importantly, treatment with rapamycin, an mTORC1 inhibitor, increased infectious virus production, while JR-AB2-011, an mTORC2 inhibitor, reduced infectious virus production. Taken together, these data demonstrate that BPLF1’s effect on the mTOR signaling cascade regulates cellular and viral processes during EBV infectivity and replication. Full article

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

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23 pages, 2674 KB

Open AccessArticle

Isolation of New Chemical Modulators of the Interaction Between HIV-1 Integrase and the Cellular Restriction Factor GCN2

by Chloé Torres, Floriane Lagadec, Eugenia Basyuk, Patricia Recordon-Pinson and Mathieu Métifiot

Viruses 2025, 17(8), 1138; https://doi.org/10.3390/v17081138 - 20 Aug 2025

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Abstract

Integrase is a key protein during HIV-1 replication as it catalyzes the integration of viral DNA into the host DNA. After several decades of research, highly potent and selective active site inhibitors have emerged. The new challenge is now to develop molecules with [...] Read more.

Integrase is a key protein during HIV-1 replication as it catalyzes the integration of viral DNA into the host DNA. After several decades of research, highly potent and selective active site inhibitors have emerged. The new challenge is now to develop molecules with an original mode of action, targeting integrase out of its catalytic site. During a previous study, we developed an in vitro assay to monitor the interaction between HIV-1 integrase and one of its cellular partners, GCN2. This AlphaLISA-based assay was validated as a platform for chemical modulator screening. In the present study, we used a library of natural products from the Developmental Therapeutics Program (NIH) to identify novel chemical leads. The best modulators were characterized and a structure–activity relationship study was initiated with a limited number of derivatives. We found that most inhibitors were tricylic or tetraclyclic molecules, with the most potent belonging to the anthracyclines/anthraquinones. Of note, several molecules exhibited interesting cellular activities and may be suitable for further optimization. Full article

(This article belongs to the Special Issue Integrase Inhibitors 2023)

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31 pages, 2627 KB

Open AccessReview

Effects of Primary Viruses (PCV2, PPV1, and PRRSV) Involved in Porcine Reproductive Failure as Mono- and Coinfections with Each Other and with Emerging Viruses (PCV3 and nPPVs)

by Diana S. Vargas-Bermudez, Jose Dario Mogollon and Jairo Jaime

Viruses 2025, 17(8), 1137; https://doi.org/10.3390/v17081137 - 19 Aug 2025

Viewed by 557

Abstract

Porcine reproductive failure (PRF) is a complex that affects reproductive parameters, leading to significant economic losses for intensive swine farms worldwide. The causes of PRF involve multiple infectious agents, classified into two main groups: primary or putative viruses, which include PCV2, PPV1, and [...] Read more.

Porcine reproductive failure (PRF) is a complex that affects reproductive parameters, leading to significant economic losses for intensive swine farms worldwide. The causes of PRF involve multiple infectious agents, classified into two main groups: primary or putative viruses, which include PCV2, PPV1, and PRRSV, and secondary or occasional viruses, such as PCV3, PCV4, and the new parvoviruses (nPPVs, PPV2 through PPV8). This review provides an updated overview of both viral groups, detailing their unique characteristics and the most commonly reported clinical signs and lesions linked to the putative viruses. While the impact of primary viruses on PRF is well established, the role of secondary viruses in PRF is still under investigation. PCV3 has been directly associated with PRF, characterized by proposed histopathological lesions. Although PCV4 has been identified in reproductive samples, its role in PRF remains unclear. Additionally, nPPVs have been found in reproductive tissues; however, a clear causal relationship with PRF has not been established. The sporadic presence of nPPVs raises questions about their direct impact on PRF and whether they may have synergistic effects when combined with other viruses. This review highlights the growing importance of viral coinfections in the context of PRF. To date, the most frequently reported coinfections are PCV2/PRRSV and PCV2/PPV1, along with emerging pairings such as PCV2/PCV3 and combinations of these two PCVs with nPPVs. Based on the existing literature and our recent findings, we propose a subclinical presentation of PRF, characterized by the presence of both primary and secondary viruses in asymptomatic sows with low viral loads. Furthermore, the synergistic effects of these viruses could contribute to a clinical form of the disease. Full article

(This article belongs to the Section Animal Viruses)

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15 pages, 3957 KB

Open AccessArticle

V4020 Venezuelan Equine Encephalitis Vaccine: Mitigating Neuroinvasion and Reversion Through Rational Design

by Adrian Centers, Koji Barnaby, Sidney Goedeker, Ava Pignataro, Irina Tretyakova, Igor Lukashevich, Peter Pushko and Donghoon Chung

Viruses 2025, 17(8), 1136; https://doi.org/10.3390/v17081136 - 19 Aug 2025

Viewed by 477

Abstract

There is a need for safe and effective vaccines against the Venezuelan equine encephalitis virus that infects both humans and equines. However, development of a live-attenuated vaccine using the TC-83 strain has been hampered by substantial reactogenicity and the potential for neuroinvasion. In [...] Read more.

There is a need for safe and effective vaccines against the Venezuelan equine encephalitis virus that infects both humans and equines. However, development of a live-attenuated vaccine using the TC-83 strain has been hampered by substantial reactogenicity and the potential for neuroinvasion. In this study, we demonstrate that V4020, a new TC-83-based investigational VEEV vaccine with redundant safety features preventing neuroinvasion and reversion, exhibited no neuroinvasion potential in a murine model. Following subcutaneous or intramuscular administration, a subset of mice that received the TC-83 vaccine succumbed to central nervous system infection, with replicating virus detected in the CNS, demonstrating a low, yet detectable neuroinvasion potential of the TC-83 vaccine in vivo. Sequencing analysis of the TC-83 virus recovered from the brains identified a pseudoreversion of E2 R120I, as E2 R120 is known to confer attenuation for TC-83. In contrast, V4020 showed no evidence of virus in the CNS, highlighting one of the V4020 features, a new synonymous codon to minimize reversion to the wild-type residue. Overall, our study establishes V4020 as a rationally designed, safe vaccine candidate for VEEV with significantly reduced neuroinvasion risk. Full article

(This article belongs to the Special Issue Mosquito-Borne Encephalitis Viruses)

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23 pages, 522 KB

Open AccessArticle

Disseminated Varicella-Zoster Virus Infection with Internal Organ Involvement: A Scoping Review of 156 Cases

by Aleksandar Timotijevic, Pratyusha Kodela, Vladislav Glušac, Sara Bokonjic, Bojan Joksimovic, Juan Vera Gomez, David Ladin and Igor Dumic

Viruses 2025, 17(8), 1135; https://doi.org/10.3390/v17081135 - 19 Aug 2025

Viewed by 717

Abstract

Visceral disseminated varicella-zoster virus infection (VD-VZV) involves the hematogenous spread of VZV from the skin to the internal organs. Though rare, it is potentially life-threatening, predominantly affecting immunocompromised individuals. Diagnosis is often delayed due to nonspecific symptoms mimicking other viral illnesses. While the [...] Read more.

Visceral disseminated varicella-zoster virus infection (VD-VZV) involves the hematogenous spread of VZV from the skin to the internal organs. Though rare, it is potentially life-threatening, predominantly affecting immunocompromised individuals. Diagnosis is often delayed due to nonspecific symptoms mimicking other viral illnesses. While the vesicular rash is a hallmark sign, it is absent in approximately 5% of cases. Visceral involvement may precede cutaneous lesions, complicate early recognition, and increase the risk of severe complications. This scoping review screened 594 articles of which 153 met the inclusion criteria, yielding 156 individual cases. Patients were predominantly male (53.8%), with a mean age of 42.3 years. The overall mortality rate was 25.0%. Multiple organs were involved in 46.1% of cases. The most frequently affected were the lungs (56%), liver (44%), heart (16%), kidneys (11%), pancreas (11%), stomach (10%), and esophagus (6%). Antivirals were administered in 89.1% of cases, while corticosteroids were used in 22.4%, with no significant impact on outcomes. Early diagnosis, achieved in 65.4% of patients, was significantly associated with survival (p = 0.043). Mortality was significantly associated with underlying comorbidities (p = 0.004), especially autoimmune diseases requiring immunosuppression (p = 0.048). Septic shock or multi-organ dysfunction (MODS), hepatitis, acute kidney injury, and acute liver failure were linked to higher mortality in univariate analysis. Multivariate analysis identified comorbidities (p < 0.001), septic shock/MODS (p = 0.008), and acute liver failure (p = 0.039) as independent predictors of mortality. Patients with septic shock/MODS had over twice the risk of death (OR = 2.24; p = 0.008). This review underscores the diagnostic challenges and high mortality of VD-VZV. Early recognition and timely administration of antiviral treatment appear critical for survival. Greater clinical awareness and further research are needed to guide management. Full article

(This article belongs to the Special Issue Herpesviruses and Associated Diseases)

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15 pages, 1929 KB

Open AccessArticle

Direct oHSV Infection Induces DC Maturation and a Tumor Therapeutic Response

by Doyeon Kim, Michael Kelly, Jack Hedberg, Alexia K. Martin, Ilse Hernandez-Aguirre, Yeaseul Kim, Lily R. Cain, Ravi Dhital and Kevin A. Cassady

Viruses 2025, 17(8), 1134; https://doi.org/10.3390/v17081134 - 19 Aug 2025

Viewed by 544

Abstract

Oncolytic herpes simplex virus (oHSV) is a promising cancer immunotherapy that induces tumor cell lysis and stimulates anti-tumor immunity. Our previous single-cell RNA sequencing analysis of oHSV-treated medulloblastoma tumors revealed expansion and activation of tumor-infiltrating dendritic cells (DCs), and direct oHSV infection of [...] Read more.

Oncolytic herpes simplex virus (oHSV) is a promising cancer immunotherapy that induces tumor cell lysis and stimulates anti-tumor immunity. Our previous single-cell RNA sequencing analysis of oHSV-treated medulloblastoma tumors revealed expansion and activation of tumor-infiltrating dendritic cells (DCs), and direct oHSV infection of DCs within the brain. While the therapeutic effects of oHSVs have been primarily attributed to tumor cell infection, we hypothesize that direct infection of DCs also contributes to therapeutic efficacy by promoting DC maturation and immune activation. Although the oHSV infection in DCs was abortive, it led to increased expression of major histocompatibility complex (MHC) class I/II and co-stimulatory molecules. oHSV-infected DCs activated naïve CD4⁺ and CD8⁺ T cells, inducing expression of CD69 and CD25. These primed T cells exhibited enhanced cytotoxicity against CT-2A glioma cells. Adoptive transfer of oHSV-infected DCs via subcutaneous injection near inguinal lymph nodes delayed tumor growth in a syngeneic CT-2A glioma model, independent of tumor viral replication and lysis. Mechanistically, our in vitro studies demonstrate that oHSV can directly infect and functionally activate DCs, enabling them to prime effective anti-tumor T cell responses. This study highlights the anti-tumor potential of leveraging oHSV-infected DCs to augment viroimmunotherapy as a cancer therapeutic. Full article

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

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1 pages, 125 KB

Open AccessRetraction

RETRACTED: Kulanayake et al. Role of Protein VII in the Production of Infectious Bovine Adenovirus-3 Virion. Viruses 2024, 16, 1323

by Shermila Kulanayake, Barinder Singh, Faryal Dar and Suresh K. Tikoo

Viruses 2025, 17(8), 1133; https://doi.org/10.3390/v17081133 - 19 Aug 2025

Viewed by 444

Abstract

The journal retracts the article “Role of Protein VII in the Production of Infectious Bovine Adenovirus-3 Virion” [...] Full article

(This article belongs to the Section Animal Viruses)

15 pages, 10651 KB

Open AccessArticle

Systemic Inflammatory Burden Causes Liver Injury in H1N1-Infected Mice

by Junbin Wang, Qing Huang, Yun Yang, Cong Tang, Wenhai Yu, Yanan Zhou, Daoju Wu, Bai Li, Hao Yang, Haixuan Wang, Lei Ma and Shuaiyao Lu

Viruses 2025, 17(8), 1132; https://doi.org/10.3390/v17081132 - 18 Aug 2025

Viewed by 425

Abstract

Clinical evidence has associated H1N1 influenza with liver impairment, yet the underlying mechanisms remain poorly understood. Here, we investigated H1N1-induced liver damage and its potential mechanisms using a BALB/c mouse infection model. Pathological examination and serum aspartate transaminase (AST) and alanine transaminase (ALT) [...] Read more.

Clinical evidence has associated H1N1 influenza with liver impairment, yet the underlying mechanisms remain poorly understood. Here, we investigated H1N1-induced liver damage and its potential mechanisms using a BALB/c mouse infection model. Pathological examination and serum aspartate transaminase (AST) and alanine transaminase (ALT) were assessed. Messenger ribonucleic acid-sequence was used to analyze the transcriptomic changes in tissues. Multiple inflammatory cytokines in tissues and inflammatory cells in the blood were detected on the fifth day post-infection. Our results showed that H1N1 infection caused significant liver pathology and elevated serum AST/ALT levels. Transcriptomic analysis revealed significant alterations in liver gene expression profiles following H1N1 infection, particularly in genes associated with inflammatory responses, including those involved in monocyte adhesion/activation and neutrophil/macrophage infiltration. Marked increases in inflammatory mediators were observed in lungs, serum, and liver, accompanied by systemic changes in circulating inflammatory cells, indicating H1N1 triggered a robust systemic inflammatory response. These findings suggest that H1N1-induced liver damage may be associated with the systemic inflammatory response induced by H1N1 and changes in liver gene regulation. Full article

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

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10 pages, 521 KB

Open AccessArticle

Detection of Influenza and Other Respiratory Pathogens by RT-qPCR and Characterization by Genomic Sequencing Using ILI/SARI Hospital-Based Sentinel Surveillance System

by Charity A. Nassuna, Fahim Yiga, Joweria Nakaseegu, Esther Amwine, Bridget Nakamoga, Noel Ayuro, Nicholas Owor, David Odongo, Jocelyn Kiconco, Thomas Nsibambi, Samuel Wasike, Ben Andagalu, Chelsea Harrington, Adam W. Crawley, Julius Ssempiira, Ray Ransom, Amy L. Boore, Barnabas Bakamutumaho, John T. Kayiwa and Julius J. Lutwama

Viruses 2025, 17(8), 1131; https://doi.org/10.3390/v17081131 - 18 Aug 2025

Viewed by 575

Abstract

Limited surveillance and laboratory testing for non-influenza viruses remains a challenge in Uganda. The World Health Organization (WHO) designated National Influenza Center (NIC) tested samples from patients with influenza-like illness (ILI) and severe acute respiratory infections (SARIs) during August 2022–February 2023. We leveraged [...] Read more.

Limited surveillance and laboratory testing for non-influenza viruses remains a challenge in Uganda. The World Health Organization (WHO) designated National Influenza Center (NIC) tested samples from patients with influenza-like illness (ILI) and severe acute respiratory infections (SARIs) during August 2022–February 2023. We leveraged the influenza sentinel surveillance system to detect other respiratory viruses (ORVs). Samples were tested using the US Centers for Disease Control and Prevention (CDC) influenza and SARS-CoV-2 multiplex and the FTD^TM Respiratory Pathogens 21 assays using real-time reverse transcription polymerase chain reaction (RT-qPCR). A total of 687 (ILI = 471 (68.6%) and SARI = 216 (31.4%) samples were tested. The median age was 2 years (IQR: 1–25) for ILI and 6 years (IQR: 1–18) for SARI case definitions (p-value = 0.045). One or more respiratory pathogens were detected in 38.7% (n = 266) of all samples; 33 (12.4%) were selected for metagenomics sequencing and 8 (3%) for SARS-CoV-2 targeted sequencing. Respiratory pathogens were detected by sequencing in 23 of 33 (69.7%) samples. Our study provides insight into the usefulness of this surveillance system in conducting virological testing for other viruses and provides tools and evidence to monitor patterns and characteristics of viruses causing ILI/SARI, which will guide public health decisions and interventions in Uganda. Full article

(This article belongs to the Special Issue Molecular Epidemiology, Evolution, and Transmission of Avian Influenza Viruses)

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16 pages, 2800 KB

Open AccessArticle

High Concordance Between SYBR Green and TaqMan PCR for SARS-CoV-2 Detection in Nasopharyngeal and Saliva Samples

by Muhareva Raekiansyah, Ratika Rahmasari, Fathan Baihaqy, Muhamad Irhamsyah, Nurul Izza Fajriani, Mila Meilani Putri, Botefilia Maharani, Rani Sauriasari, Takeshi Urano, Mya Myat Ngwe Tun and Kouichi Morita

Viruses 2025, 17(8), 1130; https://doi.org/10.3390/v17081130 - 18 Aug 2025

Viewed by 572

Abstract

During the COVID-19 pandemic, the standard diagnostic assay for SARS-CoV-2 detection was RT-qPCR using TaqMan probes, with samples primarily taken through nasal and oropharyngeal swabs. The TaqMan-based method is costly, highlighting the need for a more affordable alternative for SARS-CoV-2 diagnosis. As an [...] Read more.

During the COVID-19 pandemic, the standard diagnostic assay for SARS-CoV-2 detection was RT-qPCR using TaqMan probes, with samples primarily taken through nasal and oropharyngeal swabs. The TaqMan-based method is costly, highlighting the need for a more affordable alternative for SARS-CoV-2 diagnosis. As an alternative strategy, we developed and evaluated a SYBR Green-based RT-qPCR method targeting the RNA-dependent RNA polymerase (RdRp) gene of SARS-CoV-2. Under optimized RT-qPCR conditions, the sensitivity and linearity of the SYBR assays were assessed by using in vitro-transcribed RNA and RNA extracted from cultured SARS-CoV-2 isolates of the Wuhan reference strain and various circulating variants. Our results demonstrated that the SYBR Green-based RT-qPCR method was successfully developed with sufficient performance. The assay could detect up to 25 copies of in vitro-transcript RNA per reaction. Meanwhile, using the RNA extracted from cultured virus, the SYBR green assay was able to detect virus concentrations at least as low as 1 PFU/mL per reaction for all the variants tested. When tested on clinically relevant samples (88 naso-oropharyngeal swabs and 47 saliva samples), comparable results with the TaqMan assay were demonstrated. The Ct values of both methods for the positively detected samples were similar, with a difference in Ct of 0.72 ± 0.83 (p = 0.392) and −0.7765 ± 0.6107 (p = 0.209) for naso-oropharyngeal swab and saliva samples, respectively. These findings suggest that the SYBR method is reliable and thus offers an alternative assay for the detection of SARS-CoV-2. In particular, using saliva specimens could allow this assay to serve as a simple approach for SARS-CoV-2 detection. Full article

(This article belongs to the Section Coronaviruses)

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19 pages, 2719 KB

Open AccessArticle

Next-Generation Sequencing Analysis for HIV-1 Genotyping and Drug Resistance Mutations Mapping in Sicily, Italy

by Luca Pipitò, Sara Cannella, Chiara Mascarella, Domenico Graceffa, Marcello Trizzino, Chiara Iaria, Pietro Colletti, Giovanni Mazzola, Giovanni M. Giammanco, Antonio Cascio, Celestino Bonura and Sicilian GRT Working Group

Viruses 2025, 17(8), 1129; https://doi.org/10.3390/v17081129 - 18 Aug 2025

Viewed by 524

Abstract

Background: The advent and continuous improvement in antiretroviral therapy (ART) have profoundly altered the clinical course of HIV infection, shifting the focus from AIDS-related complications to the management of age-related comorbidities and non-AIDS-related hospitalizations. In this evolving context, optimizing ART is essential, with [...] Read more.

Background: The advent and continuous improvement in antiretroviral therapy (ART) have profoundly altered the clinical course of HIV infection, shifting the focus from AIDS-related complications to the management of age-related comorbidities and non-AIDS-related hospitalizations. In this evolving context, optimizing ART is essential, with genotypic resistance testing (GRT), particularly through next-generation sequencing (NGS), playing a pivotal role. Methods: This multicenter, retrospective cross-sectional study investigated HIV-1 subtypes, resistance mutations, and drug resistance profiles among 367 people living with HIV (PLWH) in Sicily, based on 384 GRTs performed at the Microbiology Laboratory of the University Hospital of Palermo. Results: Subtype B was the most prevalent (50%), followed by circulating recombinant forms (30%). Among treatment-naïve individuals, resistance-associated mutations were infrequent, with prevalence rates of 0.4% for NRTIs, 5.5% for NNRTIs, 1.3% for PIs, and 0.8% for INIs. Conversely, treatment-experienced individuals showed significantly higher resistance rates, especially to NRTIs (16.3%), NNRTIs (10.6%), and INIs (9.6%). No significant differences in resistance patterns were observed between B and non-B subtypes. Conclusions: This study provides the first regional overview of HIV drug resistance across Sicily. Despite the detection of resistance-associated mutations, the overall prevalence of clinically relevant resistance, particularly to currently recommended therapies, remains low, especially among treatment-naïve individuals. Full article

(This article belongs to the Special Issue Antiviral Resistance Mutations)

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20 pages, 1904 KB

Open AccessReview

Pharmacological and Adjunctive Management of Non-Hospitalized COVID-19 Patients During the Omicron Era: A Systematic Review and Meta-Analysis

by Lorenzo Vittorio Rindi, Drieda Zaçe, Loredana Sarmati, Roberto Parrella, Gianluca Russo, Massimo Andreoni and Claudio Maria Mastroianni

Viruses 2025, 17(8), 1128; https://doi.org/10.3390/v17081128 - 16 Aug 2025

Viewed by 867

Abstract

Introduction: The emergence of SARS-CoV-2 Omicron subvariants characterized by increased transmissibility and immune escape has raised concerns about the efficacy of current treatments. This systematic review and meta-analysis evaluated pharmacological and non-pharmacological interventions in Omicron-infected non-hospitalized patients, focusing on key clinical outcomes such [...] Read more.

Introduction: The emergence of SARS-CoV-2 Omicron subvariants characterized by increased transmissibility and immune escape has raised concerns about the efficacy of current treatments. This systematic review and meta-analysis evaluated pharmacological and non-pharmacological interventions in Omicron-infected non-hospitalized patients, focusing on key clinical outcomes such as hospitalization, respiratory failure, ICU admission, and 30-day mortality. Methods: Searches were performed in MEDLINE, EMBASE, Web of Science, Cochrane, and ClinicalTrials.gov (last update: 13 July 2025). Eligible studies reported outcomes on antiviral agents, monoclonal antibodies, adjunctive therapies, or telemedicine. Random-effects meta-analyses were conducted when appropriate, with heterogeneity assessed by I². Publication bias was evaluated via funnel plots and Egger’s test. Subgroup analyses explored sources of heterogeneity. Results: Eighty-eight studies were included. Meta-analyses, comparing treatment vs. no treatment, revealed that nirmatrelvir/ritonavir reduced hospitalization by 52% (RR 0.48, 95% CI 0.36–0.63) and all-cause mortality by 84% (RR 0.16, 95% CI 0.11–0.24). Remdesivir reduced hospitalization by 70% (RR 0.30, 95% CI 0.19–0.47) and respiratory failure by 89% (RR 0.11, 95% CI 0.03–0.44). Sotrovimab decreased hospitalization (RR 0.71, 95% CI 0.54–0.93) and mortality (RR 0.34, 95% CI 0.19–0.61). Molnupiravir modestly reduced hospitalization (RR 0.80, 95% CI 0.70–0.91) and respiratory failure (RR 0.45, 95% CI 0.27–0.77). Conclusions: Nirmatrelvir/ritonavir and remdesivir remain important for reducing severe outcomes, while sotrovimab retains partial efficacy. Rapid access to antivirals remains an important factor in mitigating SARS-CoV-2’s burden. Full article

(This article belongs to the Section Coronaviruses)

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20 pages, 2452 KB

Open AccessArticle

The Importance of Solution Studies for the Structural Characterization of the Enterovirus 5’ Cloverleaf

by Morgan G. Daniels, Meagan E. Werner, Xiaobing Zuo and Steven M. Pascal

Viruses 2025, 17(8), 1127; https://doi.org/10.3390/v17081127 - 16 Aug 2025

Viewed by 519

Abstract

Enteroviruses initiate genomic replication via a highly conserved mechanism that is controlled by an RNA platform, also known as the 5’ cloverleaf (5’CL). Here, we present a biophysical analysis of the 5’CL conformation of three enterovirus serotypes under various ionic conditions, utilizing CD [...] Read more.

Enteroviruses initiate genomic replication via a highly conserved mechanism that is controlled by an RNA platform, also known as the 5’ cloverleaf (5’CL). Here, we present a biophysical analysis of the 5’CL conformation of three enterovirus serotypes under various ionic conditions, utilizing CD spectroscopy, size-exclusion chromatography, and small-angle X-ray scattering. In general, a tendency toward a smaller monomeric hydrodynamic radius in the presence of salts was observed, but the exact structural signature of each 5’CL varied depending upon the serotype. Rhinovirus B14 (RVB14) exhibited at least two monomeric conformations and a low propensity for dimerization, while poliovirus 1 (PV1) showed a high propensity for dimerization, which was enhanced by the presence of salts. Enterovirus D70 was observed to be somewhat intermediate, with primarily a monomeric structure, but possessing some potential for dimerization. The equilibrium between the two monomeric and the dimeric conformations is also discussed. These results indicate that the 5’CL conformation may be more complex than the current literature suggests, thus underscoring the need for a combined crystal and solution approach for the accurate representation of the 5’CL conformation, and the conformation of other RNA structural elements, under native conditions. Full article

(This article belongs to the Special Issue An Update on Enterovirus Research, 2nd Edition)

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15 pages, 935 KB

Open AccessArticle

Integrating Serological and Genomic Data to Elucidate Lumpy Skin Disease Virus Diversity in Cattle from Bangladesh

by Nasrin Sultana Tonu, Sajedul Hayat, Shukes Chandra Badhy, Salima Ferdows, Md. Golam Azam Chowdhury, Babu Kanti Nath, Md Safiul Alam Bhuiyan, Muhammad Jasim Uddin, Suman Das Gupta and Subir Sarker

Viruses 2025, 17(8), 1126; https://doi.org/10.3390/v17081126 - 15 Aug 2025

Viewed by 557

Abstract

Lumpy skin disease virus (LSDV), a transboundary pathogen threatening cattle health in South and Southeast Asia, presents growing challenges for disease control. This study combined serological, molecular, and genomic approaches to investigate LSDV in Barura Upazila, Bangladesh. Serological screening of 424 cattle using [...] Read more.

Lumpy skin disease virus (LSDV), a transboundary pathogen threatening cattle health in South and Southeast Asia, presents growing challenges for disease control. This study combined serological, molecular, and genomic approaches to investigate LSDV in Barura Upazila, Bangladesh. Serological screening of 424 cattle using a commercial ELISA revealed a high seroprevalence of 55.5% (95% CI: 50.7–60.3), indicating widespread exposure. Although differences were observed by age and breed, no significant associations were found with seropositivity, suggesting broad regional circulation. Real-time PCR confirmed LSDV DNA in all 20 clinically infected animals, with consistent P32 gene amplification. Two samples with low Cq values underwent whole-genome sequencing. The complete genomes of LSDV-L2/2024 and LSDV-L3/2024 showed >99.6% identity with the reference strain LSDV-29, yet carried unique genomic features, including truncated or variant ORFs and immune-related gene differences. Phylogenetic analysis of the DNA polymerase gene revealed distinct clustering: L2/2024 aligned with South Asian isolates, while L3/2024 grouped with strains from Africa, the Middle East, and Europe. These results highlight co-circulation of genetically diverse strains and possible cross-regional introductions. Overall, our findings underscore the evolutionary plasticity of LSDV and the critical need for ongoing genomic surveillance to guide targeted vaccine development and disease control strategies. Full article

(This article belongs to the Section Animal Viruses)

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15 pages, 4767 KB

Open AccessArticle

First Report of the Yezo Virus Isolates Detection in Russia

by Mikhail Kartashov, Kirill Svirin, Alina Zheleznova, Alexey Yanshin, Nikita Radchenko, Valentina Kurushina, Tatyana Tregubchak, Lada Maksimenko, Mariya Sivay, Vladimir Ternovoi, Alexander Agafonov and Anastasia Gladysheva

Viruses 2025, 17(8), 1125; https://doi.org/10.3390/v17081125 - 15 Aug 2025

Viewed by 670

Abstract

The recent discovery of the Yezo virus (YEZV) in Japan and China has raised particular concern due to its potential to cause human diseases ranging from mild febrile illnesses to severe neurological disorders. We report, for the first time, the detection of five [...] Read more.

The recent discovery of the Yezo virus (YEZV) in Japan and China has raised particular concern due to its potential to cause human diseases ranging from mild febrile illnesses to severe neurological disorders. We report, for the first time, the detection of five YEZV isolates in I. persulcatus ticks from three regions of Russia. The analysis was performed using 5318 ticks of two Ixodes genus collected in 2024 from 23 regions of Russia. The minimum infection rate of YEZV in Russia among I. persulcatus ticks was 0.12% (95% CI: 0.05–0.28). The westernmost and northernmost YEZV detection points have been recorded. YEZV isolates circulating in Russia are genetically diverse. Protein domains of Russian YEZV isolates’ genomes were characterized using HMMER, AlphaFold 3, and InterProScan. The YEZV nucleoprotein (N) of Russian isolates has a racket-shaped structure with “head” and “stalk” domains similar to those of Orthonairovirus haemorrhagiae. The Lys261–Arg261 substitution in the YEZV N Chita 2024-1 isolate occurs in the α11 structure in the region of interaction with viral RNA. Our results show that the distribution area of YEZV is much wider than previously known, provide new data on complete YEZV genomes, extend our structural insight into YEZV N, and suggest a potential target for antiviral drug development to treat YEZV infection. Full article

(This article belongs to the Special Issue Tick-Borne Viruses: Transmission and Surveillance, 2nd Edition)

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14 pages, 15804 KB

Open AccessArticle

Herpes Simplex 2 Virus Depletes Cells of DEAD-Box Helicase 3 Protein by Packaging It into Virions

by Carmen Rita Piazza, Giulia Lottini, Paola Quaranta, Paola Perrera, Fabio Filippini, Michele Lai, Cristina Di Primio, Giulia Freer and Mauro Pistello

Viruses 2025, 17(8), 1124; https://doi.org/10.3390/v17081124 - 15 Aug 2025

Viewed by 615

Abstract

Human DEAD-box helicase 3 (DDX3) is a multifunctional RNA helicase implicated in mRNA unwinding and the regulation of gene expression. While DDX3 has been extensively studied in the context of RNA virus replication, its role in DNA virus replication remains less understood. In [...] Read more.

Human DEAD-box helicase 3 (DDX3) is a multifunctional RNA helicase implicated in mRNA unwinding and the regulation of gene expression. While DDX3 has been extensively studied in the context of RNA virus replication, its role in DNA virus replication remains less understood. In this study, we explore the involvement of DDX3 in the life cycle of Herpes Simplex Virus type 2 (HSV-2), a double-stranded DNA virus. Silencing of DDX3 expression with siRNA significantly impaired HSV-2 replication, indicating that DDX3 supports viral propagation. Unexpectedly, HSV-2 infection led to a marked reduction in cellular DDX3 protein levels during in vitro replication in human cells, particularly at 24 h post-infection, corresponding to the peak of viral production. Notably, this decrease was not accompanied by a reduction in DDX3 mRNA levels, nor was it prevented by proteasome inhibition, suggesting an alternative mechanism of DDX3 depletion. Further analysis revealed substantial amounts of DDX3 protein within HSV-2 virions, supporting the hypothesis that DDX3 is packaged into viral particles during replication. We propose that HSV-2 exploits host DDX3 by incorporating it into progeny virions to facilitate early stages of infection in newly infected cells. However, no evidence linking DDX3 to the assembly process of HSV-2 particles was found. These findings expand the known functional repertoire of DDX3 and highlight its potential as a host factor co-opted by DNA viruses, suggesting a broader relevance in antiviral strategies. Full article

(This article belongs to the Section Animal Viruses)

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12 pages, 1465 KB

Open AccessArticle

Development and Application of Mouse-Derived CD2v Monoclonal Antibodies Against African Swine Fever Virus from Single B Cells

by Litao Yu, Fangtao Li, Xingqi Zou, Lu Xu, Junjie Zhao, Yan Li, Guorui Peng, Yingju Xia, Qizu Zhao and Yuanyuan Zhu

Viruses 2025, 17(8), 1123; https://doi.org/10.3390/v17081123 - 15 Aug 2025

Viewed by 535

Abstract

African swine fever (ASF) is a highly pathogenic and hemorrhagic swine infectious disease caused by the African swine fever virus (ASFV). It encodes over 150 proteins, among which the CD2v protein plays multiple roles throughout the infection process. Single B-cell antibody technology is [...] Read more.

African swine fever (ASF) is a highly pathogenic and hemorrhagic swine infectious disease caused by the African swine fever virus (ASFV). It encodes over 150 proteins, among which the CD2v protein plays multiple roles throughout the infection process. Single B-cell antibody technology is a cutting-edge method for preparing monoclonal antibodies (mAbs), which has the advantages of rapid, efficient, and high yield in antibody production, while possessing natural conformations. In this study, by cloning and expressing antibody genes in vitro, 14 murine-derived mAbs were prepared using recombinant CD2v proteins as immunogenic sources, which brings sufficient enrichment and selectivity for the development of antibodies based on the single B-cell antibody technique. All 14 mAbs demonstrated reactivity with CD2v protein by indirect ELISA, whereas 8 mAbs successfully detected CD2v in ASFV-infected PAM cells by IFA, indicating the tested mAbs can effectively recognize and bind to ASFV CD2v. Finally, a blocking ELISA method for detecting CD2v antibodies using CD2v mAb C89 was established, which holds significant potential for broad application in the serological diagnosis of ASFV with determination of the CD2v-blocking ELISA specificity, sensitivity, reproducibility, and compliance rate. It could be used for the rapid clinical detection of ASFV CD2v protein to provide a powerful tool for the monitoring of epidemics. Full article

(This article belongs to the Special Issue Swine Viruses: Immunology and Vaccinology)

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28 pages, 3103 KB

Open AccessArticle

First Complete Genome Sequence of Palo Verde Broom Emaravirus, Virus-Derived siRNA Signatures, and Phytohormone-Metabolite Profiling of Witches’ Broom-Affected Palo Verde Trees

by Raphael O. Adegbola, Muhammad Ilyas, Dinusha C. Maheepala, Ursula K. Schuch and Judith K. Brown

Viruses 2025, 17(8), 1122; https://doi.org/10.3390/v17081122 - 15 Aug 2025

Viewed by 520

Abstract

Witches’ broom disease of blue palo verde (Parkinsonia florida) was reported more than sixty years ago. Characteristic symptoms consist of dense clusters of shortened, brittle branches and stunted leaves. The suspect causal agent has been identified as palo verde broom virus [...] Read more.

Witches’ broom disease of blue palo verde (Parkinsonia florida) was reported more than sixty years ago. Characteristic symptoms consist of dense clusters of shortened, brittle branches and stunted leaves. The suspect causal agent has been identified as palo verde broom virus (PVBV), genus, Emaravirus, family, Fimoviridae. Here, the first complete PVBV genome sequence was determined, and virus small interfering RNAs (vsiRNAs), primary metabolites, and phytohormone profiles were characterized from infected palo verde leaves, adventitious shoots, flowers, and seeds. Based on pairwise distances, PVBV RNAs 1–4 shared 54–65% nucleotide identity and 19–51% amino acid similarity, respectively, with other emaraviruses, while PVBV RNA 5 shared no sequence homology with any emaravirus. The 21–24-nt virus-derived vsiRNAs, indicative of post-transcriptional gene silencing (PTGS), represented nearly the entire PVBV genome in flowers, leaves, seeds, and adventitious shoots; however, PVBV RNA 3 and RNA 4 were most heavily targeted in all plant parts. Evidence that six major phytohormones were altered in PVBV-infected compared to virus-free trees indicated that emaravirus-infected trees mount classical defense responses to virus infection and/or eriophyid mite infestations. Detection of PVBV RNA genome segments 1–5, accumulation of predominantly 21-nt vsiRNAs, homologous to the PVBV genome and transcripts, and altered levels of phytohormones and metabolites in PVBV-infected trees strongly implicate PVBV as the causal agent of witches’ broom disease. Full article

(This article belongs to the Special Issue Emerging and Re-Emerging Plant Viruses and Vector Complexes: Advances in Characterization, Surveillance, and Mitigation)

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15 pages, 455 KB

Open AccessArticle

White-Tailed Deer Prion Protein Gene Variability Suggests Selection Against Chronic Wasting Disease in Canada’s Prairies

by William Pilot, Maria I. Arifin, Antanas Staskevicius, Nicholas J. Haley, Gordon Mitchell and Jiewen Guan

Viruses 2025, 17(8), 1121; https://doi.org/10.3390/v17081121 - 15 Aug 2025

Viewed by 571

Abstract

Chronic wasting disease (CWD), a transmissible spongiform encephalopathy that targets cervids, has become a significant threat to both free-ranging and captive populations of Canadian white-tailed deer. In an effort to mitigate its spread, research in the past 20 years has demonstrated that the [...] Read more.

Chronic wasting disease (CWD), a transmissible spongiform encephalopathy that targets cervids, has become a significant threat to both free-ranging and captive populations of Canadian white-tailed deer. In an effort to mitigate its spread, research in the past 20 years has demonstrated that the genetic background of deer may influence the pathogenesis of CWD. Specifically, variants located on the 95-, 96-, 116- and 226-codon of the prion protein gene seem to attenuate disease progression in white-tailed deer. The influence of these alleles on the likelihood of being found CWD-positive on Saskatchewan and Albertan farms was assessed using a Bayesian logistic regression model. To assess the presence of selection for favourable prion protein gene alleles, shifts in variant genotype frequencies were examined over the last seventeen years. Our results show that deer harboring the G96S allele have significantly lowered odds of infection within Canadian herds. Furthermore, the prevalence of this allele has increased significantly in farmed deer over the past seventeen years. Establishing the dynamic genetic background of Canadian deer populations will inform future disease management initiatives. Full article

(This article belongs to the Special Issue Chronic Wasting Disease: From Pathogenesis to Prevention)

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17 pages, 18176 KB

Open AccessArticle

Identification and Structural Characterization of Viroporins from Deadly Hemorrhagic Viruses

by Hiya Lahiri, Kingshuk Basu and Isaiah T. Arkin

Viruses 2025, 17(8), 1120; https://doi.org/10.3390/v17081120 - 14 Aug 2025

Viewed by 597

Abstract

Crimean–Congo hemorrhagic fever virus (CCHF-V) and Ebola virus are lethal pathogens that cause widespread outbreaks of hemorrhagic fever. Both diseases can be transmitted through contact with the bodily fluids of infected individuals, but as an arbovirus, CCHF-V is primarily transmitted through tick bites. [...] Read more.

Crimean–Congo hemorrhagic fever virus (CCHF-V) and Ebola virus are lethal pathogens that cause widespread outbreaks of hemorrhagic fever. Both diseases can be transmitted through contact with the bodily fluids of infected individuals, but as an arbovirus, CCHF-V is primarily transmitted through tick bites. Both of these viruses are classified as Risk Group 4 due to the appreciable health threat they pose. To date, there are few effective treatments available to combat these deadly hemorrhagic fevers. Consequently, identifying and characterizing ion channels (viroporins) encoded in the viral genomes may lead to potential targeted drug development. Therefore, using bacteria-based genetic assays, two viroporin candidates from CCHF-V and Ebola have been examined, and their proposed structures have been modeled to aid in further drug discovery. The results indicate that CCHF-V-gp exhibits channel activity, which is indistinguishable from established viroporins found in other viruses. In contrast, our experimental approach was unable to uncover a viroporin candidate in the Ebola virus. Full article

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

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12 pages, 821 KB

Open AccessArticle

The Clinical and Laboratory Predictors of Intensive Care Unit Admission in Romanian Measles Cases: A Retrospective Cohort Analysis (2023–2025)

by Aneta-Rada Dobrin, Tamara Mirela Porosnicu, Islam Ragab, Lucian-Flavius Herlo, Voichita Elena Lazureanu, Alexandra Herlo, Felix Bratosin, Cristian Iulian Oancea, Silvia Alda and Monica Licker

Viruses 2025, 17(8), 1119; https://doi.org/10.3390/v17081119 - 14 Aug 2025

Viewed by 490

Abstract

Background and Objectives: Romania has experienced the highest measles incidence rate in the European Union since late 2023, driven by suboptimal measles–mumps–rubella (MMR) uptake. Contemporary data on bedside predictors of clinical deterioration are scarce. The objective was to characterise demographic, clinical and [...] Read more.

Background and Objectives: Romania has experienced the highest measles incidence rate in the European Union since late 2023, driven by suboptimal measles–mumps–rubella (MMR) uptake. Contemporary data on bedside predictors of clinical deterioration are scarce. The objective was to characterise demographic, clinical and laboratory differences between severe and non-severe measles and derive a multivariable model for intensive-care-unit (ICU) admission. Methods: We undertook a retrospective cohort study at the “Victor Babeș” University Hospital for Infectious Diseases, Timișoara. All admissions from 1 November 2023 to 15 May 2025 with serological or RT-PCR confirmation and a complete baseline laboratory panel were included. Descriptive statistics compared ward-managed versus ICU-managed patients; independent predictors of ICU transfer were identified through logistic regression that incorporated age, vaccination status, leukocyte count, C-reactive protein (CRP) and interleukin-6 (IL-6). Results: Among 455 patients (median age 3.0 y, interquartile range [IQR] 1.0–7.0), 17 (3.7%) required ICU care. Vaccine coverage was 18.0% overall and 0% among ICU cases. Compared with ward peers, ICU patients exhibited higher leukocyte counts (8.1 × 10⁹ L vs. 6.0 × 10⁹ L; p = 0.003) and a near-five-fold elevation in IL-6 (18 pg mL vs. 4 pg mL; p < 0.001), while CRP, procalcitonin and fibrinogen were similar. ICU admission prolonged median length of stay from 5 days (IQR 4–7) to 8 days (5–12; p = 0.004). In multivariable modelling, IL-6 remained the sole independent predictor (odds ratio [OR] 1.07 per pg mL; 95% confidence interval [CI] 1.03–1.12; p = 0.001); the model’s AUC was 0.83, indicating good discrimination. Complete separation precluded reliable estimation of the protective effect of vaccination, but no vaccinated child required ICU care. Conclusions: A simple admission panel centred on IL-6 accurately identified Romanian measles patients at risk of critical deterioration, whereas traditional markers such as CRP and leukocyte count added little incremental value. Even a single documented MMR dose was associated with the complete absence of ICU transfers, underscoring the urgent need for catch-up immunisation campaigns. Integrating IL-6-guided triage with intensified vaccination outreach could substantially reduce measles-related morbidity and health-system strain in low-coverage EU settings. Full article

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

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Viruses, Volume 17, Issue 8 (August 2025) – 127 articles

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