Viruses

16 pages, 3629 KiB

Open AccessArticle

Ten Previously Unassigned Human Cosavirus Genotypes Detected in Feces of Children with Non-Polio Acute Flaccid Paralysis in Nigeria in 2020

by Toluwani Goodnews Ajileye, Toluwanimi Emmanuel Akinleye, Temitope O. C. Faleye, Lander De Coninck, Uwem Etop George, Anyebe Bernard Onoja, Sheriff Tunde Agbaje, Ijeoma Maryjoy Ifeorah, Oluseyi Adebowale Olayinka, Elijah Igbekele Oni, Arthur Obinna Oragwa, Bolutife Olubukola Popoola, Olaitan Titilola Olayinka, Oluwadamilola Gideon Osasona, Oluwadamilola Adefunke George, Philip G. Ajayi, Adedolapo A. Suleiman, Ahmed Iluoreh Muhammad, Isaac Komolafe, Adekunle Johnson Adeniji, Jelle Matthijnssens and Moses Olubusuyi Adewumi Show full author list Hide full author list

Viruses 2025, 17(6), 844; https://doi.org/10.3390/v17060844 (registering DOI) - 12 Jun 2025

Abstract

Since its discovery via metagenomics in 2008, human cosavirus (HCoSV) has been detected in the cerebrospinal fluid (CSF) and feces of humans with meningitis, acute flaccid paralysis (AFP), and acute gastroenteritis. To date, 34 HCoSV genotypes have been documented by the Picornaviridae study [...] Read more.

Since its discovery via metagenomics in 2008, human cosavirus (HCoSV) has been detected in the cerebrospinal fluid (CSF) and feces of humans with meningitis, acute flaccid paralysis (AFP), and acute gastroenteritis. To date, 34 HCoSV genotypes have been documented by the Picornaviridae study group. However, the documented genetic diversity of HCoSV in Nigeria is limited. Here we describe the genetic diversity of HCoSV in Nigeria using a metagenomics approach. Archived and anonymized fecal specimens from children (under 15 years old) diagnosed with non-polio AFP from five states in Nigeria were analyzed. Virus-like particles were purified from 55 pools (made from 254 samples) using the NetoVIR protocol. Pools were subjected to nucleic acid extraction and metagenomic sequencing. Reads were trimmed and assembled, and contigs classified as HCoSV were subjected to phylogenetic, pairwise identity, recombination analysis, and, when necessary, immuno-informatics and capsid structure prediction. Fifteen pools yielded 23 genomes of HCoSV. Phylogenetic and pairwise identity analysis showed that all belonged to four species (eleven, three, three, and six members of Cosavirus asiani, Cosavirus bepakis, Cosavirus depakis, and Cosavirus eaustrali, respectively) and seventeen genotypes. Ten genomes belong to seven (HCoSV-A3/A10, A15, A17, A19, A24, D3, and E1) previously assigned genotypes, while the remaining thirteen genomes belonged to ten newly proposed genotypes across the four HCoSV species, based on the near-complete VP1 region (VP1*) of the cosavirus genome. Our analysis suggests the existence of at least seven and eight Cosavirus bepakis and Cosavirus eaustrali genotypes, respectively (including those described here). We report the first near-complete genomes of Cosavirus bepakis and Cosavirus depakis from Nigeria, which contributes to the increasing knowledge of the diversity of HCoSV, raising the number of tentative genotypes from 34 to over 40. Our findings suggest that the genetic diversity of HCoSV might be broader than is currently documented, highlighting the need for enhanced surveillance. Full article

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

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11 pages, 520 KiB

Open AccessArticle

Prevalence of Hepatitis C in the Emilia-Romagna Region of Italy: Population-Wide Screening

by Gianmarco Imperiali, Matteo Fiore, Alessandro Bianconi, Giovanna Mattei, Giulio Matteo, Giuseppe Diegoli, Esther Rita De Gioia, Cecilia Acuti Martellucci, Maria Elena Flacco, Lamberto Manzoli and Regional HCV Working Group

Viruses 2025, 17(6), 843; https://doi.org/10.3390/v17060843 - 12 Jun 2025

Abstract

In agreement with WHO recommendations, the Emilia-Romagna Region, Italy, implemented a population-wide HCV screening program for the treatment of the large asymptomatic infected population. From January 2022, the free-of-charge screening targeted all residents born between 1969 and 1989, prison inmates, and injection drug [...] Read more.

In agreement with WHO recommendations, the Emilia-Romagna Region, Italy, implemented a population-wide HCV screening program for the treatment of the large asymptomatic infected population. From January 2022, the free-of-charge screening targeted all residents born between 1969 and 1989, prison inmates, and injection drug users. Participants were recruited using phone messages, electronic health record notifications, public advertisement, and direct contact with general practitioners. A single blood sample was collected for anti-HCV IgG testing and, if positive, for reflex HCV–RNA testing. Infected subjects were offered an evidence-based therapeutic pathway. By June 2024, 72.8% of high-risk subjects (n = 19,732), and 36.9% of the general population (n = 488,065) had been screened. A total of 1032 individuals were positive based on the HCV–RNA test, and the detection rate widely differed between the high-risk and the general population (23.8‰ vs. 1.2‰, respectively). Of the infected individuals, 88.1% were seen by a specialist physician, and 74.3% (n = 767) started antiviral therapy. Thanks to multiple recruitment approaches, over one third of the general population participated in HCV screening. The program performance was substantially greater among high-risk individuals compared to the general population. To achieve WHO targets, policymakers might consider expanding the screening to other high-risk subgroups and/or adapting birth cohorts. Full article

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

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18 pages, 2111 KiB

Open AccessArticle

Consensus Sequences for Gag and Pol Introduced into HIV-1 Clade B Laboratory Strains Differentially Influence the Impact of Point Mutations Associated with Immune Escape and with Drug Resistance on Viral Replicative Capacity

by Sven Breitschwerdt, Benedikt Grandel, Benedikt Asbach, Franziska Winter, Todd Allen, Ralf Wagner, Bernd Salzberger and Arne Schneidewind

Viruses 2025, 17(6), 842; https://doi.org/10.3390/v17060842 - 12 Jun 2025

Abstract

Viral evasion from effective human immunodeficiency virus type 1 (HIV-1)-specific CD8+ T-cell responses and from antiretroviral therapy through viral sequence variation is frequently accompanied by a loss in viral fitness. The impact of sequence variations on replication capacity in vitro was mostly studied [...] Read more.

Viral evasion from effective human immunodeficiency virus type 1 (HIV-1)-specific CD8+ T-cell responses and from antiretroviral therapy through viral sequence variation is frequently accompanied by a loss in viral fitness. The impact of sequence variations on replication capacity in vitro was mostly studied by introducing single mutations into a specific clonal strain such as NL4-3. How the specific viral backbone itself impacts replicative fitness remains elusive. To test for a potential effect of the viral backbone, we constructed HIV-1 clade B clones with consensus sequences for gag and/or pol and evaluated the infectivity of viral variants harboring well-defined cytotoxic T-lymphocyte (CTL) escape mutations or drug resistance mutations within this backbone or the clonal NL4-3 strain. Viral variants with consensus sequences were replication-competent in vitro, although at lower rates than the NL4-3 virus. Introduction of the dominant CTL escape mutation R₂₆₄K into the newly constructed viruses or into NL4-3 led to a dramatic reduction in infection rates. In contrast to the NL4-3 backbone, the combination of R₂₆₄K with its compensatory mutation S₁₇₃A on the consensus backbone led to higher infection rates as compared to the same virus in the absence of R₂₆₄K and S₁₇₃A. Furthermore, 2 out of 10 drug resistance mutations in pol led to opposing effects, with an increase in infection rates on the consensus gag/pol backbone and a reduction on NL4-3. Therefore, the effect of the respective viral backbone on infectivity observed in vitro might constitute an additional factor to explain differential kinetics of mutational evasion from immune and pharmaceutical pressure. Full article

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

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13 pages, 2677 KiB

Open AccessArticle

A Single-Tube Two-Step MIRA-CRISPR/Cas12b Assay for the Rapid Detection of Mpox Virus

by Ge Hu, Zhijie Wei, Jinlei Guo, Kangchen Zhao, Qiao Qiao, Xiaojuan Zhu, Tao Wu, Heng Rong, Shuo Ning, Ziyang Hao, Ying Chi, Lunbiao Cui and Yiyue Ge

Viruses 2025, 17(6), 841; https://doi.org/10.3390/v17060841 - 12 Jun 2025

Abstract

Mpox is a zoonotic disease caused by the Mpox virus (MPXV). The rapid and accurate diagnosis of MPXV is essential for the timely and effective prevention, control, and treatment of the disease. In this study, we combined Multienzyme Isothermal Rapid Amplification (MIRA) (at [...] Read more.

Mpox is a zoonotic disease caused by the Mpox virus (MPXV). The rapid and accurate diagnosis of MPXV is essential for the timely and effective prevention, control, and treatment of the disease. In this study, we combined Multienzyme Isothermal Rapid Amplification (MIRA) (at 42 °C) and Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein 12b(CRISPR/Cas12b) (at 60 °C) to develop a single-tube two-step assay for rapid MPXV detection, leveraging the distinct physical states of tricosane at these temperatures. MIRA amplification primers and CRISPR/cas12b SgRNA were designed based on the MPXV F3L gene. After screening the primers and sgRNAs, the reaction conditions were optimized, and the performances of the assay were evaluated. The detection limit (LOD) of this single-tube two-step MIRA-CRISPR/Cas12b assay for MPXV is four copies of DNA molecules. No cross-reactivity with other pathogens (herpes simplex virus (HSV), Epstein–Barr virus (EBV), Coxsackievirus A16 (CVA16), Enterovirus A71 (EV-A71), and measles virus (MeV)) was found. The assay also showed good consistency with quantitative real-time PCR (qPCR) (Kappa = 0.9547, p < 0.05, n = 100) in the detection of clinical samples, with a sensitivity of 98.5% and a specificity of 97.0%. The single-tube two-step MIRA-CRISPR/Cas12b assay permits the rapid (within 45 min), sensitive, and specific detection of MPXV. The lack of need for opening the reaction tube eliminates the risk of product contamination. Full article

(This article belongs to the Section General Virology)

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16 pages, 2095 KiB

Open AccessArticle

Identification of Clinical and Genomic Features Associated with SARS-CoV-2 Reinfections

by Francisco Muñoz-López, Antoni E. Bordoy, Francesc Català-Moll, Verónica Saludes, David Panisello Yagüe, Mariona Parera, Ignacio Blanco, Pere-Joan Cardona, Cristina Casañ, Ana Blanco-Suárez, Sandra Franco, Álvaro F. García-Jiménez, Roger Paredes, Bonaventura Clotet, Lourdes Mateu, Marc Noguera-Julian, Elisa Martró, José Ramón Santos and Marta Massanella

Viruses 2025, 17(6), 840; https://doi.org/10.3390/v17060840 (registering DOI) - 11 Jun 2025

Abstract

Although SARS-CoV-2 reinfections remain a concern for healthcare systems worldwide, the factors driving them are still not fully understood. In this study, we examined data for 3303 individuals who experienced two SARS-CoV-2 infections between March 2020 and May 2022 from both clinical and [...] Read more.

Although SARS-CoV-2 reinfections remain a concern for healthcare systems worldwide, the factors driving them are still not fully understood. In this study, we examined data for 3303 individuals who experienced two SARS-CoV-2 infections between March 2020 and May 2022 from both clinical and viral genomics perspectives. Our findings indicate that viral evolution was the primary driver of reinfection. However, chronic conditions were common among reinfected individuals, including those under 26 years old, suggesting that the presence of underlying and/or chronic conditions increases susceptibility to reinfection. The median time elapsed between infections was one year, often coinciding with the emergence of new variants. While vaccination showed only a limited protective effect against reinfection, it drastically decreased the hospitalization rate, underscoring its role in mitigating disease severity. Our findings point to the need for more flexible vaccination strategies, especially for individuals with chronic conditions. Understanding the interactions between host factors and viral evolution is critical to strengthening prevention strategies and reducing the burden of reinfections and their possible long-term complications. Full article

(This article belongs to the Special Issue Emerging Variants of SARS-CoV-2)

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22 pages, 1569 KiB

Open AccessReview

HIV, Inflammation, and Immunometabolism: A Model of the Inflammatory Theory of Disease

by Eman Teer, Nyasha C. Mukonowenzou and M. Faadiel Essop

Viruses 2025, 17(6), 839; https://doi.org/10.3390/v17060839 - 11 Jun 2025

Abstract

Inflammation is a crucial component of the immune response essential for host defense and tissue repair. However, when the immune response becomes dysregulated, it can contribute to the pathogenesis of chronic diseases. While acute inflammation is a short-lived, protective response, chronic inflammation is [...] Read more.

Inflammation is a crucial component of the immune response essential for host defense and tissue repair. However, when the immune response becomes dysregulated, it can contribute to the pathogenesis of chronic diseases. While acute inflammation is a short-lived, protective response, chronic inflammation is sustained over time and can lead to immune dysfunction, tissue damage, and disease progression. The chronic inflammation theory of disease suggests that persistent immune activation/inflammation underlies both infectious and non-infectious conditions and serves as a unifying mechanism across distinct pathological states. In this review article, we argue that human immunodeficiency virus (HIV) infection represents a prime model for studying chronic inflammation, and that despite effective viral suppression with antiretroviral therapy (ART), people living with HIV (PLWH) exhibit persistent immune activation, systemic inflammation, and an increased risk of cardiovascular, metabolic, and neurodegenerative diseases. Here, the interplay between microbial translocation, immune dysregulation, and metabolic reprogramming fuels a state of chronic inflammation that accelerates disease progression beyond HIV itself. Key factors such as T-cell exhaustion, persistent monocyte/macrophage activation, and immunometabolic dysfunction contribute to such a sustained inflammatory state. This review explores the molecular and cellular mechanisms driving chronic inflammation in HIV infection with a focus on immunometabolism and its implications for broader inflammatory diseases. By understanding such pathways, we can identify novel therapeutic targets to mitigate inflammation-driven disease progression not only in HIV but across a spectrum of chronic inflammatory conditions. Full article

(This article belongs to the Special Issue Viral Infections and Immune Dysregulation 2024–2025)

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21 pages, 4768 KiB

Open AccessArticle

Differential Expression of Host miRNAs During Ad14 and Ad14p1 Infection

by Eric R. McIndoo, Ethan Wood, Gina Kuffel, Michael J. Zilliox and Jay R. Radke

Viruses 2025, 17(6), 838; https://doi.org/10.3390/v17060838 - 11 Jun 2025

Abstract

Adenovirus is a frequent cause of mild, usually self-limited infections in infants and young children. Severe infections occur in immunocompromised patients but are rarely observed in healthy, immunocompetent adults. However, there have been outbreaks of infections with different adenoviral (Ad) types around the [...] Read more.

Adenovirus is a frequent cause of mild, usually self-limited infections in infants and young children. Severe infections occur in immunocompromised patients but are rarely observed in healthy, immunocompetent adults. However, there have been outbreaks of infections with different adenoviral (Ad) types around the world that have resulted in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in some of those infected. Ad14p1 is the predominant circulating strain of Ad14 worldwide that has caused ARDS. An explanation for the severity of illness caused by Ad14p1 infection in immunocompetent patients is unknown. Previously, we have shown that A549 cells infected with Ad14 repress macrophage pro-inflammatory responses, whereas cells infected with Ad14p1 fail to repress macrophages and instead can increase pro-inflammatory responses. Adenoviral infection has been shown to modulate host miRNA expression, and we hypothesized that differences in miRNA expression between Ad14- and Ad14p1-infected cells might explain the differential responses of macrophages to Ad14- and Ad14p1-infected cells. Analysis of host miRNA showed that 98 miRNAs are differentially expressed when infection reaches full cytopathic effect (CPE), the same point at which Ad14 and Ad14p1 CPE corpses induce differential inflammatory responses in macrophages. Only 10 of the miRNAs that were enriched in Ad14 CPE corpses were expressed at levels that are potentially biologically relevant. Pathway enrichment analysis showed that the differentially expressed miRNAs might explain the increased pathogenesis of Ad14p1 through strain-related loss of modulation of cytokine expression when compared with prototype Ad14. Overall, the data suggest a role for viral regulation of host miRNA expression in pathogenesis by regulating host inflammatory responses through the delivery of de-regulated miRNAs by viral CPE corpses to macrophages. Full article

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

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18 pages, 1237 KiB

Open AccessArticle

Serological Surveillance of Betacoronaviruses in Bat Guano Collectors: Pre-COVID-19 Pandemic and Post-SARS-CoV-2 Emergence

by Sasiprapa Ninwattana, Spencer L. Sterling, Khwankamon Rattanatumhi, Nattakarn Thippamom, Piyapha Hirunpatrawong, Pakamas Sangsub, Thaniwan Cheun-Arom, Dominic Esposito, Chee Wah Tan, Wee Chee Yap, Feng Zhu, Lin-Fa Wang, Eric D. Laing, Supaporn Wacharapluesadee and Opass Putcharoen

Viruses 2025, 17(6), 837; https://doi.org/10.3390/v17060837 - 10 Jun 2025

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Abstract

Community-based serosurveillance for emerging zoonotic viruses can provide a powerful and cost-effective measurement of cryptic spillovers. Betacoronaviruses, including SARS-CoV, SARS-CoV-2 and MERS-CoV, are known to infect bats and can cause severe respiratory illness in humans, yet remain under-surveyed in high-risk populations. This study [...] Read more.

Community-based serosurveillance for emerging zoonotic viruses can provide a powerful and cost-effective measurement of cryptic spillovers. Betacoronaviruses, including SARS-CoV, SARS-CoV-2 and MERS-CoV, are known to infect bats and can cause severe respiratory illness in humans, yet remain under-surveyed in high-risk populations. This study aimed to determine the seroprevalence of betacoronaviruses in an occupational cohort in contact with bats before and after the emergence of SARS-CoV-2. Serum samples from pre- and post-COVID-19 pandemic were screened using antigen-based multiplex microsphere immunoassays (MMIAs) and a multiplex surrogate virus neutralization test (sVNT). Pre-pandemic samples showed no SARS-CoV-2 antibodies, while post-pandemic samples from vaccinated participants displayed binding and neutralizing antibodies against SARS-CoV-2 and a related bat CoV. Furthermore, one participant (1/237, 0.43%) had persistent antibodies against MERS-CoV in 2017, 2018 and 2021 but was seronegative in 2023, despite reporting no history of traveling abroad or severe pneumonia. The observed sustained antibody levels indicate a possible exposure to MERS-CoV or a MERS-CoV-like virus, although the etiology and clinical relevance of this finding remains unclear. Ongoing surveillance in high-risk populations remains crucial for understanding virus epidemiology and mitigating zoonotic transmission risk. Full article

(This article belongs to the Section Coronaviruses)

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24 pages, 4480 KiB

Open AccessArticle

Pharmacokinetics and Metabolism of Broad-Spectrum Antivirals Remdesivir and Obeldesivir with a Consideration to Metabolite GS-441524: Same, Similar, or Different?

by Darius Babusis, Cynthia Kim, Jesse Yang, Xiaofeng Zhao, Guoju Geng, Carmen Ip, Nathan Kozon, Hoa Le, Jennifer Leung, Jared Pitts, Dustin S. Siegel, Rao Kalla, Bernard Murray, John P. Bilello, Roy Bannister, Richard L. Mackman and Raju Subramanian

Viruses 2025, 17(6), 836; https://doi.org/10.3390/v17060836 - 10 Jun 2025

Viewed by 209

Abstract

RNA viruses with pandemic potential pose a significant global health risk. The adenosine nucleoside analog GS-441524 is metabolized to its active GS-443902 triphosphate metabolite to inhibit a broad spectrum of RNA viruses. Intravenous (IV) remdesivir (RDV) and oral obeldesivir (ODV) are phosphoramidate and [...] Read more.

RNA viruses with pandemic potential pose a significant global health risk. The adenosine nucleoside analog GS-441524 is metabolized to its active GS-443902 triphosphate metabolite to inhibit a broad spectrum of RNA viruses. Intravenous (IV) remdesivir (RDV) and oral obeldesivir (ODV) are phosphoramidate and isobutyryl-ester prodrugs of GS-441524, respectively. Following administration, both RDV and ODV show rapid and broad tissue distribution, form the same GS-443902 metabolite in target tissues, and demonstrate promising in vivo efficacy across several RNA virus infection models. In an African green monkey SARS-CoV-2 infection model, respective RDV and ODV treatments yielded similar antiviral efficacy. Here, we compare the in vitro and in vivo pharmacokinetics (PK) and metabolism of RDV and ODV to highlight both similarities and differences in their absorption, metabolism, distribution, and excretion profiles. The distinct route of administration and metabolic fate of each prodrug produced in vivo PK and metabolism profiles with differential GS-441524 to tissue GS-443902 relationships, thereby supporting alternate methods for predicting human efficacious doses. Overall, a metabolism-directed prodrug design enabled optimized delivery of the identical active GS-443902 metabolite through different routes of administration, supporting broader applications of the same nucleoside analog across an expanded spectrum of potential antiviral indications. Full article

(This article belongs to the Special Issue Viral Replication Inhibitors)

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33 pages, 4537 KiB

Open AccessReview

The Use of Intrinsic Disorder and Phosphorylation by Oncogenic Viral Proteins to Dysregulate the Host Cell Cycle Through Interaction with pRb

by Heidi Kast-Woelbern, Sarah K. Martinho, Kayla T. Julio, Audrey M. Vazzana, Abbey E. Mandagie and Ariane L. Jansma

Viruses 2025, 17(6), 835; https://doi.org/10.3390/v17060835 - 10 Jun 2025

Viewed by 279

Abstract

Approximately 15% of cancers worldwide are caused by oncogenic viruses. These infectious agents utilize multiple strategies to dysregulate their host cells as a means of viral reproduction. While this typically involves a small number of viral oncoproteins known to interact with a myriad [...] Read more.

Approximately 15% of cancers worldwide are caused by oncogenic viruses. These infectious agents utilize multiple strategies to dysregulate their host cells as a means of viral reproduction. While this typically involves a small number of viral oncoproteins known to interact with a myriad of host cell proteins, direct binding with the tumor suppressor retinoblastoma protein (pRb) as a means to dysregulate the cell cycle appears to be a common mechanism among most known oncogenic viruses. This review evaluates the shared structural themes of binding motif, intrinsic disorder, and viral oncoprotein phosphorylation, utilized by eight different oncogenic viruses for the subjugation of pRb. Cancer caused by oncogenic viruses represents one of the few potentially preventable forms of cancer. The more we understand the common strategies used by these infectious agents, the better equipped we will be to further optimize vaccination and therapeutic strategies to fight them. Full article

(This article belongs to the Special Issue Viral Oncogenes)

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15 pages, 690 KiB

Open AccessReview

The Role of Bacteriophage-Derived Small RNA Molecules in Bacterial and Phage Interactions

by Natalia Lewandowska, Sylwia Bloch, Aleksandra Łukasiak, Wojciech Wesołowski, Grzegorz Węgrzyn and Bożena Nejman-Faleńczyk

Viruses 2025, 17(6), 834; https://doi.org/10.3390/v17060834 - 10 Jun 2025

Viewed by 150

Abstract

Small regulatory RNAs (sRNAs) play a critical role in bacterial gene expression, modulating various cellular processes, including stress responses, metabolism, virulence, and many others. While well-characterized in bacterial systems, an emerging class of phage-derived sRNAs has been identified, suggesting an underexplored regulatory network [...] Read more.

Small regulatory RNAs (sRNAs) play a critical role in bacterial gene expression, modulating various cellular processes, including stress responses, metabolism, virulence, and many others. While well-characterized in bacterial systems, an emerging class of phage-derived sRNAs has been identified, suggesting an underexplored regulatory network at phage–host interactions. These sRNAs, encoded within phage genomes, influence both bacterial and viral life cycles by modulating transcriptional and post-transcriptional gene expression processes. The interplay between phage-derived sRNAs and the host genome reveals a complex network of gene regulation, with an impact on bacterial fitness, pathogenesis, and horizontal gene transfer. This review explores the diverse functions of phage-encoded sRNAs, highlighting recent discoveries and their impact on bacterial physiology and phage-host interactions. Full article

(This article belongs to the Special Issue Bacteriophage Diversity, 2nd Edition)

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12 pages, 474 KiB

Open AccessArticle

Changes in Saliva Analytes in Pigs in Different Clinical Situations from Farms Positive to Porcine Reproductive and Respiratory Syndrome (PRRS): A Pilot Study

by Eva Llamas-Amor, Silvia Martínez-Subiela, Fernando Tecles, Aida Miralles, Elena Goyena, Andrea Martínez-Martínez, José Joaquín Cerón and Alberto Muñoz-Prieto

Viruses 2025, 17(6), 833; https://doi.org/10.3390/v17060833 - 9 Jun 2025

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Abstract

Porcine reproductive and respiratory syndrome (PRRS) is aworldwide spread disease. This study analyzed the changes in saliva analytes of pigs infected with PRRS virus (PRRSV) in different clinical conditions that can appear in PRRSV-positive farms. Biomarkers for inflammation (haptoglobin, total proteins), immune response [...] Read more.

Porcine reproductive and respiratory syndrome (PRRS) is aworldwide spread disease. This study analyzed the changes in saliva analytes of pigs infected with PRRS virus (PRRSV) in different clinical conditions that can appear in PRRSV-positive farms. Biomarkers for inflammation (haptoglobin, total proteins), immune response (adenosine deaminase), tissue damage (lactate dehydrogenase), stress (alpha-amylase), and sepsis (calprotectin, aldolase, Serpin B12) were measured in pigs under three clinical scenarios: (1) no evident clinical signs, (2) clinical signs indicating PRRSV activation, and (3) secondary bacterial infection by Streptococcus suis. Haptoglobin and lactate dehydrogenase showed significant increases in pigs with PRRSV activation compared to pigs without clinical signs. Additionally, the levels of Serpin B12, aldolase, calprotectin, total proteins, and the activity of adenosine deaminase significantly increased in pigs with meningitis compared to pigs without clinical signs, but did not show significant differences between healthy pigs and those with PRRSV clinical signs without bacterial infection. In summary, PRRSV-infected pigs can show differences in selected saliva analytes depending on their clinical condition. These findings may have practical applications for detecting PRRSV infections and differentiating cases with associated meningitis. Full article

(This article belongs to the Section Animal Viruses)

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12 pages, 873 KiB

Open AccessArticle

HIV-1 Genetic Diversity and Transmitted Drug Resistance Mutations in ART-Naïve Individuals in South Korea from 2021 to 2024

by Gayeong Kim, Eun Ji Kim, Min-Seong Kim, Seolhui Kim, Heui Man Kim, Myung-Guk Han and Jin-Sook Wang

Viruses 2025, 17(6), 832; https://doi.org/10.3390/v17060832 - 9 Jun 2025

Viewed by 79

Abstract

In this study, we investigated the proportion of transmitted drug resistance (TDR) mutations and human immunodeficiency virus (HIV)-1 subtypes among 487 antiretroviral therapy (ART)-naïve individuals in South Korea from 2021 to 2024 to inform more effective treatment strategies. Consistent with previous reports, subtype [...] Read more.

In this study, we investigated the proportion of transmitted drug resistance (TDR) mutations and human immunodeficiency virus (HIV)-1 subtypes among 487 antiretroviral therapy (ART)-naïve individuals in South Korea from 2021 to 2024 to inform more effective treatment strategies. Consistent with previous reports, subtype B was most prevalent among HIV-1 subtypes at 50.7%; however, its proportion decreased annually (p = 0.047). Various subtypes of circulating recombinant forms (CRFs) were analyzed in this study, resulting in high genetic diversity. The subtype distributions of Korean and non-Korean patients differed, with subtype B (53.7%) and CRF01_AE (34.4%) being dominant in the former and latter, respectively. TDR across antiretroviral drug classes was approximately 3.5% in South Korea. Non-nucleoside reverse transcriptase inhibitors elicited the greatest drug resistance, which increased from 2021 to 2023, with a slight decrease in 2024. The integrase strand transfer inhibitor drugs, elvitegravir and raltegravir, most frequently exhibited high resistance scores. We provide a comprehensive overview of the HIV-1 genetic distribution and TDR patterns in South Korea from 2021 to 2024. Within the broader context of HIV-1 epidemiology in Asia and the Pacific, the findings contribute to a comprehensive understanding of the global distribution of HIV-1 resistance and genotypes, enabling the development of effective interventions. Full article

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

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18 pages, 4438 KiB

Open AccessArticle

Strain-Divergent m6A Landscapes Modulate Nipah Virus Replication and METTL3 Inhibition Attenuates Virulence

by Ting Luo, Zhen Chen, Fang Zhang, Haibin Liu, Fang Huang, Xueyan Zhang, Jiangpeng Feng, Shuang Ding, Lishi Liu, Wuxiang Guan, Aiping Zeng and Haojie Hao

Viruses 2025, 17(6), 831; https://doi.org/10.3390/v17060831 - 9 Jun 2025

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Abstract

Nipah virus (NiV), a highly lethal zoonotic paramyxovirus, displays strain-specific pathogenicity, yet the molecular basis for this divergence remains elusive. Here, we identify N6-methyladenosine (m6A) modification as a pivotal regulator of NiV replication. Higher m6A methylation levels on viral genomic RNA and mRNAs [...] Read more.

Nipah virus (NiV), a highly lethal zoonotic paramyxovirus, displays strain-specific pathogenicity, yet the molecular basis for this divergence remains elusive. Here, we identify N6-methyladenosine (m6A) modification as a pivotal regulator of NiV replication. Higher m6A methylation levels on viral genomic RNA and mRNAs are associated with the increased virulence observed in the NiV-Malaysia (NiV-M) strain compared to NiV-Bangladesh (NiV-B). Underlying this phenomenon, NiV infection orchestrates a reprogramming of the host m6A machinery by downregulating the methyltransferase METTL3 and the demethylase ALKBH5, while concurrently upregulating m6A reader proteins YTHDF1-3. Both METTL3 and ALKBH5 bind directly to NiV RNA, with METTL3 installing m6A to promote viral replication and ALKBH5 removing them to inhibit it. Strikingly, pharmacological inhibition of m6A modification markedly attenuates NiV replication in vitro and in vivo, underscoring the therapeutic potential of targeting the m6A pathway. Our study establishes m6A as a key determinant of NiV pathogenicity and provides a paradigm for host-directed antiviral strategies against high-risk RNA viruses. Full article

(This article belongs to the Section Animal Viruses)

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11 pages, 2347 KiB

Open AccessCommunication

Discovery of a Rodent Hepacivirus in the Brazilian Amazon

by Nelielma G. Oliveira Prestes, Leonardo H. Almeida Hernández, Fábio Silva da Silva, Thito Y. Bezerra da Paz, Andressa O. Aragão, Bruno C. Veloso de Barros, Ricardo J. P. S. Guimarães, Rommel T. J. Ramos, Lívia Medeiros Neves Casseb, Sandro Patroca da Silva, Pedro Fernando da Costa Vasconcelos and Ana Cecília Ribeiro Cruz

Viruses 2025, 17(6), 830; https://doi.org/10.3390/v17060830 - 8 Jun 2025

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Abstract

In the eastern Brazilian Amazon, the Viseu municipality has almost 70% of its territory deforested. Monitoring viruses from wildlife hosts enables the prevention and control of epizootic events and outbreaks. Seven samples from three marsupials and two rodents were screened by high-throughput sequencing [...] Read more.

In the eastern Brazilian Amazon, the Viseu municipality has almost 70% of its territory deforested. Monitoring viruses from wildlife hosts enables the prevention and control of epizootic events and outbreaks. Seven samples from three marsupials and two rodents were screened by high-throughput sequencing for virome analysis. The three samples from the two Proechimys roberti rodents, one from the liver, one from the brain, and one from a pooled viscera sample, showed the highest results in terms of viral abundance and richness. From these we obtained two strains of a new rodent hepacivirus (RHV), which belongs to a new putative genotype of an unclassified RHV species previously described in Panama and Northeast Brazil. The findings expand the host range of the cited RHV species, imply virus circulation in the study area, and suggest a viral tropism in the liver and perhaps in the brain. Full article

(This article belongs to the Special Issue Animal Virus Discovery and Genetic Diversity)

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6 pages, 670 KiB

Open AccessOpinion

Rogueing or Rescuing? A Potential New Management Approach for Roses Infected with Rose Rosette Virus

by Caleb Paslay and Akhtar Ali

Viruses 2025, 17(6), 829; https://doi.org/10.3390/v17060829 - 8 Jun 2025

Viewed by 154

Abstract

Roses (Rosa spp.) are among the most economically and culturally significant flowering plants worldwide. However, rose cultivation faces a critical threat from rose rosette disease (RRD), which is caused by Emaravirus rosae (rose rosette virus, RRV), a negative-sense RNA virus transmitted by [...] Read more.

Roses (Rosa spp.) are among the most economically and culturally significant flowering plants worldwide. However, rose cultivation faces a critical threat from rose rosette disease (RRD), which is caused by Emaravirus rosae (rose rosette virus, RRV), a negative-sense RNA virus transmitted by the eriophyid mite Phyllocoptes fructiphilus. Current RRD management strategies mainly depend on the complete removal (rogueing) of symptomatic plants, which are effective but adds high economic and aesthetic costs. During our field and laboratory observations from 2023 to 2024, we documented that RRV often remains localized to a single cane for extended periods of time (up to 80 days) in one variety before systemic spread to other canes of the same plant. This discovery supports a proposed “rescue hypothesis”, suggesting that early pruning of symptomatic canes may prevent full-plant infection and serve as a viable alternative to rogueing under specific conditions. While preliminary, our findings offer a potentially cost-effective, less destructive management strategy. However, further research is needed to validate this hypothesis and inform integrated disease management practices are established for effective control of RRD. Full article

(This article belongs to the Section Viruses of Plants, Fungi and Protozoa)

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25 pages, 7711 KiB

Open AccessArticle

Synergizing Attribute-Guided Latent Space Exploration (AGLSE) with Classical Molecular Simulations to Design Potent Pep-Magnet Peptide Inhibitors to Abrogate SARS-CoV-2 Host Cell Entry

by Farhan Ullah, Aobo Xiao, Shahid Ullah, Na Yang, Min Lei, Liang Chen and Sheng Wang

Viruses 2025, 17(6), 828; https://doi.org/10.3390/v17060828 - 7 Jun 2025

Viewed by 335

Abstract

The COVID-19 infection, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has evoked a worldwide pandemic. Even though vaccines have been developed on an enormous scale, but due to regular mutations in the viral gene and the emergence of new strains could [...] Read more.

The COVID-19 infection, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has evoked a worldwide pandemic. Even though vaccines have been developed on an enormous scale, but due to regular mutations in the viral gene and the emergence of new strains could pose a more significant problem for the population. Therefore, new treatments are always necessary to combat future pandemics. Utilizing an antiviral peptide as a model biomolecule, we trained a generative deep learning algorithm on a database of known antiviral peptides to design novel peptide sequences with antiviral activity. Using artificial intelligence (AI), specifically variational autoencoders (VAE) and Wasserstein autoencoders (WAE), we were able to generate a latent space plot that can be surveyed for peptides with known properties and interpolated across a predictive vector between two defined points to identify novel peptides that exhibit dose-responsive antiviral activity. Two hundred peptide sequences were generated from the trained latent space and the top peptides were subjected to a molecular docking study. The docking analysis revealed that the top four peptides (MSK-1, MSK-2, MSK-3, and MSK-4) exhibited the strongest binding affinity, with docking scores of −106.4, −126.2, −125.7, and −127.8, respectively. Molecular dynamics simulations lasting 500 ns were performed to assess their stability and binding interactions. Further analyses, including MMGBSA, RMSD, RMSF, and hydrogen bond analysis, confirmed the stability and strong binding interactions of the peptide–protein complexes, suggesting that MSK-4 is a promising therapeutic agent for further development. We believe that the peptides generated through AI and MD simulations in the current study could be potential inhibitors in natural systems that can be utilized in designing therapeutic strategies against SARS-CoV-2. Full article

(This article belongs to the Special Issue Harnessing AI and Machine Learning for Antiviral Development)

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12 pages, 4737 KiB

Open AccessCommunication

Myricetin Restricts the Syncytial Development Triggered by Nipah Virus Envelope Glycoproteins In Vitro

by Ananda Murali Rayapati, Chanda Chandrasekhar, Sudarsana Poojari and Bhadra Murthy Vemulapati

Viruses 2025, 17(6), 827; https://doi.org/10.3390/v17060827 - 7 Jun 2025

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Abstract

Background and Objectives: Myricetin, a flavonoid compound, was demonstrated to effectively arrest the cell-to-cell fusion and syncytial development triggered by Nipah virus (NiV) fusion (F) and attachment (G) envelope glycoproteins in vitro involving two permissive mammalian cell lines. Methods: Time-of-addition assays were carried [...] Read more.

Background and Objectives: Myricetin, a flavonoid compound, was demonstrated to effectively arrest the cell-to-cell fusion and syncytial development triggered by Nipah virus (NiV) fusion (F) and attachment (G) envelope glycoproteins in vitro involving two permissive mammalian cell lines. Methods: Time-of-addition assays were carried out using codon-optimized NiV wild type (WT) F and G plasmids followed by a challenge with the addition of myricetin 1 h and 6 h post-transfection in HEK 293T and Vero cells. Results: Upon evaluating different myricetin concentrations, it was determined that a 100 μM concentration of myricetin effectively inhibited 64–80% of syncytia in HEK and Vero cells. Interpretation & Conclusions: In this study, we concluded that myricetin mitigated the syncytial development in HEK and Vero cell lines. Given the flavonoid attributes of myricetin which is widely present in fruits, vegetables, tea, and wine, it may be regarded as a phytonutrient and a safer antiviral alternative against Nipah virus infections. Due to the BSL-4 nature of the virus, further research involving live virus culture is necessary to confirm myricetin as a potential antiviral compound for the mitigation of pathological effects of NiV infections. Full article

(This article belongs to the Section General Virology)

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19 pages, 7764 KiB

Open AccessArticle

Binding Specificity and Oligomerization of TSWV N Protein in the Western Flower Thrips, Frankliniella occidentalis

by Falguni Khan, Eticha Abdisa, Niayesh Shahmohammadi and Yonggyun Kim

Viruses 2025, 17(6), 826; https://doi.org/10.3390/v17060826 - 7 Jun 2025

Viewed by 211

Abstract

Tomato spotted wilt virus (TSWV) is a highly destructive plant pathogen and transmitted by several thrips including the western flower thrips, Frankliniella occidentalis. A structural N protein encoded in the viral genome represents the nucleocapsid protein by binding to the viral RNA [...] Read more.

Tomato spotted wilt virus (TSWV) is a highly destructive plant pathogen and transmitted by several thrips including the western flower thrips, Frankliniella occidentalis. A structural N protein encoded in the viral genome represents the nucleocapsid protein by binding to the viral RNA genome. However, it remains unknown how the RNA-binding protein specifically interacts with the viral RNA from host RNAs in the target cells. To study the molecular basis of N function, we produced the protein in Escherichia coli and the resulting purified recombinant protein was used to investigate the protein–RNA interactions. The recombinant N protein migrated on agarose gel to the anode in the electric field due to its high basic isoelectric point. This electrostatic property led N protein to bind to DNA as well as RNA. It also bound to both single-stranded (ssRNA) and double-stranded RNA (dsRNA). However, when the total RNA was extracted from plant tissues collected from TSWV-infected host, the RNA extract using the recombinant N protein was much richer in the TSWV genome compared to that without the protein. To investigate the specificity of N protein to ssRNA, the three-dimensional structure was predicted using the AlphaFold program and showed its trimeric oligomerization with the binding pocket for ssRNA. This was supported by the differential susceptibility of N protein with ssRNA and dsRNA against RNase attack. Furthermore, a thermal shift assay to analyze the RNA and protein interaction showed that ssRNA strongly interacted with N protein compared to dsRNA. In addition, the N gene was expressed along with the multiplication of the viral RNA genome segments from the segment-specific fluorescence in situ hybridization analysis in different tissues during different developmental stages of the virus-infected F. occidentalis. These results suggest that the functional trimeric N proteins bind to the viral RNA to form a basic nucleocapsid structure at a specific virus-replicating compartment within the host cells. Full article

(This article belongs to the Special Issue Molecular Virus-Insect Interactions, 2nd Edition)

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15 pages, 773 KiB

Open AccessReview

Modulation of Plant Interactions with Whitefly and Whitefly-Borne Viruses by Salicylic Acid Signaling Pathway: A Review

by Shi-Xing Zhao, Su-Dan Wang, Yin-Quan Liu and Li-Long Pan

Viruses 2025, 17(6), 825; https://doi.org/10.3390/v17060825 - 7 Jun 2025

Viewed by 264

Abstract

Whiteflies of the Bemisia tabaci complex, along with the plant viruses they transmit, pose significant challenges to crop production worldwide. Upon infestation or infection, intimate interactions occur between plant hosts and these pests, influencing the spread and severity of pest-related epidemics in natural [...] Read more.

Whiteflies of the Bemisia tabaci complex, along with the plant viruses they transmit, pose significant challenges to crop production worldwide. Upon infestation or infection, intimate interactions occur between plant hosts and these pests, influencing the spread and severity of pest-related epidemics in natural and agricultural ecosystems. This review explores the role of the salicylic acid (SA) signaling pathway, an essential component of plant defense, in modulating plant interactions with whiteflies and whitefly-borne viruses. We first outline the biosynthesis and signal transduction of SA. We then analyze how whitefly infestation activates the SA signaling pathway and how this defense response affects whitefly performance and preference. Next, we explore the interactions between the SA signaling pathway and whitefly-borne plant viruses, especially begomoviruses, which often activate and manipulate this pathway. We also examine how the SA signaling pathway influences plant–whitefly–virus tripartite interactions, highlighting the significant role of this defense pathway in whitefly-induced changes in plant–virus interactions and virus-induced changes in plant–whitefly interactions. Finally, we identify key areas for future research to further unravel the complexities of plant interactions with whiteflies and whitefly-borne viruses. Full article

(This article belongs to the Section Viruses of Plants, Fungi and Protozoa)

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18 pages, 2815 KiB

Open AccessArticle

The Involvement of MGF505 Genes in the Long-Term Persistence of the African Swine Fever Virus in Gastropods

by Sona Hakobyan, Nane Bayramyan, Zaven Karalyan, Roza Izmailyan, Aida Avetisyan, Arpine Poghosyan, Elina Arakelova, Tigranuhi Vardanyan and Hranush Avagyan

Viruses 2025, 17(6), 824; https://doi.org/10.3390/v17060824 - 7 Jun 2025

Viewed by 216

Abstract

African swine fever virus (ASFV), a highly contagious and lethal virus affecting domestic and wild pigs, has raised global concerns due to its continued spread across Europe and Asia. While traditional transmission pathways involve suids and soft ticks, this study investigates the potential [...] Read more.

African swine fever virus (ASFV), a highly contagious and lethal virus affecting domestic and wild pigs, has raised global concerns due to its continued spread across Europe and Asia. While traditional transmission pathways involve suids and soft ticks, this study investigates the potential role of freshwater gastropods as environmental reservoirs capable of sustaining ASFV. We analysed ASFV survival in ten gastropod species after long-term co-incubation with the virus. Viral transcriptional activity, particularly of the late gene B646L and members of the multigene family MGF505, was evaluated in snail faeces up to nine weeks post-infection. Results revealed that several gastropods, including Melanoides tuberculata, Tarebia granifera, Physa fontinalis, and Pomacea bridgesii, support long-term persistence of ASFV, accompanied by increased MGF505 gene expression. Notably, the simultaneous activation of MGF5052R and MGF50511R significantly correlated with higher B646L expression and extended viral survival, suggesting a functional role in ASFV maintenance. Conversely, antiviral (AV) activity assays showed that some gastropod faeces reduced replication of the unrelated Influenza virus, hinting at induced host defences. A negative correlation was observed between AV activity and the expression of MGF505 2R/11R, implying that ASFV may suppress antiviral responses to facilitate persistence. These findings suggest that certain gastropods may serve as overlooked environmental hosts, contributing to ASFV epidemiology via long term viral shedding. Further research is needed to clarify the mechanisms underlying ASFV–host interactions and to assess the ecological and epidemiological implications of gastropods in ASFV transmission cycles. Full article

(This article belongs to the Section Animal Viruses)

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11 pages, 4768 KiB

Open AccessArticle

Identification of a Conserved Linear Epitope on the p54 Protein of African Swine Fever Virus

by Kuijing He, Yue Wu, Zhipeng Su, Yue Zeng, Guishan Ye, Qi Wu, Long Li and Anding Zhang

Viruses 2025, 17(6), 823; https://doi.org/10.3390/v17060823 - 7 Jun 2025

Viewed by 223

Abstract

African swine fever virus (ASFV) is a highly virulent pathogen that causes nearly 100% mortality in acute infections and poses persistent risks. Effective containment of ASFV outbreaks requires rapid and reliable diagnostic tools. The p54 protein, a key structural component of ASFV, has [...] Read more.

African swine fever virus (ASFV) is a highly virulent pathogen that causes nearly 100% mortality in acute infections and poses persistent risks. Effective containment of ASFV outbreaks requires rapid and reliable diagnostic tools. The p54 protein, a key structural component of ASFV, has emerged as an important target for serological detection. Herein, the recombinant p54 protein (amino acids 53–184) was expressed in Escherichia coli, and three mouse monoclonal antibodies (mAbs) (IgG1/kappa subtype) were developed. Among these mAbs, the mAb 1F9 specifically recognized the B-cell epitope ⁶⁶IQFINPYQDQQ⁷⁶, which is conserved across different genotypes of ASFV, suggesting that the epitope may serve as a valuable target for serological detection of ASFV. Structural modeling analysis revealed that this epitope is surface-exposed on the p54 protein, with ⁶⁷Gln and ⁶⁸Phe identified as critical residues for 1F9 binding. Moreover, a blocking ELISA based on the mAb 1F9 was established for detecting ASFV-specific antibodies in clinical serum samples, achieving a coincidence rate exceeding 95%. These findings demonstrate that mAb 1F9, targeting a conserved and accessible region of p54, represents a valuable tool for ASFV serodiagnosis, surveillance, and outbreak management. Full article

(This article belongs to the Section Animal Viruses)

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15 pages, 452 KiB

Open AccessArticle

Steroid Pulse Therapy Leads to Secondary Infections and Poor Outcomes in Patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Intensive Care Units: A Retrospective Cohort Study

by Katsuhiro Nakagawa, Shingo Ihara, Junko Yamaguchi, Tsukasa Kuwana and Kosaku Kinoshita

Viruses 2025, 17(6), 822; https://doi.org/10.3390/v17060822 - 6 Jun 2025

Viewed by 207

Abstract

The efficacy of steroid pulse therapy for treating severe coronavirus disease (COVID-19) pneumonia remains unclear. This study aimed to determine the efficacy of steroid pulse therapy for severe COVID-19 pneumonia in patients who did not respond to conventional therapy, including steroids. We included [...] Read more.

The efficacy of steroid pulse therapy for treating severe coronavirus disease (COVID-19) pneumonia remains unclear. This study aimed to determine the efficacy of steroid pulse therapy for severe COVID-19 pneumonia in patients who did not respond to conventional therapy, including steroids. We included 76 patients with severe COVID-19 pneumonia treated with steroids in this single-facility retrospective observational study. Severe COVID-19 pneumonia was defined as requiring high-concentration oxygen administration (oxygen mask with reservoir mask (RM) > 6 L/min), high-flow nasal cannula oxygen therapy, or ventilatory support for respiratory control. The patient characteristics at admission and changes in them over time were examined in (a) a survival vs. death group, and (b) a steroid pulse vs. non-steroid pulse therapy group. Steroid pulse therapy significantly improved the ratio of partial pressure of arterial oxygen to fraction of inspired oxygen just after the therapy and after one week of therapy, but had no effect on the sequential organ failure assessment scores over time. Multivariate logistic regression analyses showed that remdesivir use was associated with better survival outcomes, while steroid pulse therapy was associated with poor outcomes. In conclusion, steroid pulse therapy did not improve the prognosis of patients with severe COVID-19 pneumonia any more effectively than conventional steroid therapy. Full article

(This article belongs to the Special Issue COVID-19 and Pneumonia, 3rd Edition)

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20 pages, 2817 KiB

Open AccessArticle

A Versatile Reporter Platform for Evaluating HDR- and NHEJ-Based Genome Editing in Airway Epithelial Cell Cultures Using an rAAV Vector

by Soo Yeun Park, Zehua Feng, Xiujuan Zhang, Yinghua Tang, Donovan Richart, Kai E. Vorhies, Jianming Qiu, John F. Engelhardt and Ziying Yan

Viruses 2025, 17(6), 821; https://doi.org/10.3390/v17060821 - 6 Jun 2025

Viewed by 304

Abstract

Therapeutic gene editing strategies utilize endogenous DNA repair pathways—nonhomologous end joining (NHEJ) or homology-directed repair (HDR)—to introduce targeted genomic modifications. Because HDR is restricted to dividing cells, whereas NHEJ functions in both dividing and non-dividing cells, NHEJ-based approaches are better suited for in [...] Read more.

Therapeutic gene editing strategies utilize endogenous DNA repair pathways—nonhomologous end joining (NHEJ) or homology-directed repair (HDR)—to introduce targeted genomic modifications. Because HDR is restricted to dividing cells, whereas NHEJ functions in both dividing and non-dividing cells, NHEJ-based approaches are better suited for in vivo gene editing in the largely post-mitotic airway epithelium. Homology-independent targeted insertion (HITI), an NHEJ-based method, offers a promising strategy for cystic fibrosis (CF) gene therapy. Here, we applied HITI to drive the expression of a promoterless reporter through an exon trap strategy in both proliferating airway basal cells and well-differentiated primary airway epithelial cultures derived from transgenic ROSA^mTmG ferrets. We also established a versatile human gene editing reporter (GER) airway basal cell line capable of multipotent differentiation, enabling real-time visualization of editing outcomes and the quantitative assessment of HDR- and NHEJ-based editing efficiencies. Together, these platforms provide easily accessible tools for optimizing genome editing strategies in the respiratory epithelium and advancing clinically relevant delivery strategies for CF gene therapy. Full article

(This article belongs to the Special Issue Virology and Immunology of Gene Therapy 2025)

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12 pages, 682 KiB

Open AccessArticle

Neurological Manifestation of Canine Distemper Virus: Increased Risk in Young Shih Tzu and Lhasa Apso with Seasonal Prevalence in Autumn

by Heloisa L. Freire, Ítalo H. N. Iara, Luana S. R. Ribeiro, Paulo A. O. Gonçalves, David H. Matta and Bruno B. J. Torres

Viruses 2025, 17(6), 820; https://doi.org/10.3390/v17060820 - 6 Jun 2025

Viewed by 302

Abstract

Canine distemper virus (CDV) is a highly contagious disease with high morbidity and mortality rates in veterinary medicine. This retrospective study aimed to identify epidemiological characteristics and potential risk factors associated with CDV infection in dogs exhibiting neurological manifestations. The diagnosis was confirmed [...] Read more.

Canine distemper virus (CDV) is a highly contagious disease with high morbidity and mortality rates in veterinary medicine. This retrospective study aimed to identify epidemiological characteristics and potential risk factors associated with CDV infection in dogs exhibiting neurological manifestations. The diagnosis was confirmed through immunochromatographic antigen testing, RT-PCR, or Lentz corpuscles identification. Dogs diagnosed with central nervous system (CNS) disorders unrelated to CDV served as the control group. Age, breed, weight, sex, and neuter status were compared between groups using logistic regression (p < 0.05), the log-likelihood method, and log odds ratio (LOR) calculations. Clinical signs, seasonality, and vaccination protocols were documented. Prevalence, mortality, lethality, and survival rates were determined. Younger dogs (p = 0.00690; LOR = −0.01438) and Shih Tzu (p = 0.00007; LOR = 1.53774) and Lhasa Apso (p = 0.000264; LOR = 1.76084) showed a significantly increased likelihood of developing neurological signs due to CDV infection. Most CDV-infected dogs exhibited multifocal CNS involvement and accompanying extra-neural signs. The highest occurrence of CDV-related neurological signs was recorded in autumn. Many infected dogs had an updated vaccination protocol. The prevalence of dogs with CDV was 4.72%. Mortality and lethality rates were 1.94% and 47.06%, respectively. The median survival time was 754 days. The identified epidemiological characteristics and risk factors provide essential insights for improving preventive strategies against CDV infection. Full article

(This article belongs to the Special Issue Canine Distemper Virus)

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33 pages, 1491 KiB

Open AccessReview

The Evolving Role of Zika Virus Envelope Protein in Viral Entry and Pathogenesis

by Ashkan Roozitalab, Jiantao Zhang, Chenyu Zhang, Qiyi Tang and Richard Y. Zhao

Viruses 2025, 17(6), 817; https://doi.org/10.3390/v17060817 - 6 Jun 2025

Viewed by 420

Abstract

Zika virus (ZIKV) was first discovered in Uganda’s Zika Forest in 1947. The early African viruses posed little or no health risk to humans. Since then, ZIKV has undergone extensive genetic evolution and adapted to humans, and it now causes a range of [...] Read more.

Zika virus (ZIKV) was first discovered in Uganda’s Zika Forest in 1947. The early African viruses posed little or no health risk to humans. Since then, ZIKV has undergone extensive genetic evolution and adapted to humans, and it now causes a range of human diseases, including neurologically related diseases in adults and congenital malformations such as microcephaly in newborns. This raises a critical question as to why ZIKV has become pathogenic to humans, and what virological changes have taken place and enabled it to cause these diseases? This review aims to address these questions. Specifically, we focus on the ZIKV envelope (E) protein, which is essential for initiating infection and plays a crucial role in viral entry. We compare various virologic attributes of E protein between the ancestral African strains, which presumably did not cause human diseases, with epidemic strains responsible for current human pathogenesis. First, we review the role of the ZIKV E protein in viral entry and endocytosis during the viral life cycle. We will then examine how the E protein interacts with host immune responses and evades host antiviral responses. Additionally, we will analyze key differences in the sequence, structure, and post-translational modifications between African and Asian lineages, and discuss their potential impacts on viral infection and pathogenesis. Finally, we will evaluate neutralizing antibodies, small molecule inhibitors, and natural compounds that target the E protein. This will provide insights into the development of potential vaccines and antiviral therapies to prevent or treat ZIKV infections and associated diseases. Full article

(This article belongs to the Special Issue Preparation for the Next Potential Pandemic—Chikungunya, Dengue, Zika and Other Viruses)

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7 pages, 480 KiB

Open AccessConference Report

Navigating Virology’s Frontiers in Africa: Global Virus Network 2024 Durban Meeting

by Maggie L. Bartlett, Rubeshan Perumal, Sten H. Vermund and Salim Abdool Karim

Viruses 2025, 17(6), 819; https://doi.org/10.3390/v17060819 - 5 Jun 2025

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Abstract

The Global Virus Network (GVN) is a voluntary consortium of virology laboratories and affiliated scientists that seek to prevent and control global viral threats. The meetings of the GVN are characterized by academic, health center, government, and industry participation, sharing information that is [...] Read more.

The Global Virus Network (GVN) is a voluntary consortium of virology laboratories and affiliated scientists that seek to prevent and control global viral threats. The meetings of the GVN are characterized by academic, health center, government, and industry participation, sharing information that is designed to further the mutual mission. In September 2024, the meeting in Durban, South Africa, highlighted diseases and investigators from Africa, and paid special attention to pandemic preparedness. Selected highlights from the meeting are presented here, along with a call-to-action in defense of global partnerships for research in the origins of human and animal viruses, the risk to humans from other animal sources, the pathogenesis of given viruses, and their prevention and treatment. Discussions of laboratory discovery science are juxtaposed with development of vaccines, antiviral drugs, immunotherapies, and innovative field strategies for control of viral diseases. Full article

(This article belongs to the Section General Virology)

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16 pages, 809 KiB

Open AccessArticle

DENV-2 Circulation and Host Preference Among Highly Anthropophilic, Outdoor-Biting Aedes aegypti in Dar es Salaam, Tanzania

by Frank S. C. Tenywa, Silvan Hälg, Haji Makame, Jason Moore, Osward Dogan, Harubu I. Mapipi, Jane J. Machange, Nasoro S. Lilolime, Lorenz M. Hofer, Lewis D. Batao, Tunu G. Mwamlima, Pie Müller and Sarah J. Moore

Viruses 2025, 17(6), 818; https://doi.org/10.3390/v17060818 - 5 Jun 2025

Viewed by 384

Abstract

In Tanzania, dengue outbreaks have occurred almost annually over the past decade, with each new outbreak becoming more severe. This study investigated the prevalence of dengue virus (DENV) serotypes in the wild Aedes aegypti and their blood sources to determine human exposure risk [...] Read more.

In Tanzania, dengue outbreaks have occurred almost annually over the past decade, with each new outbreak becoming more severe. This study investigated the prevalence of dengue virus (DENV) serotypes in the wild Aedes aegypti and their blood sources to determine human exposure risk in Dar es Salaam, Tanzania. A two-year longitudinal survey was conducted in the Ilala, Kinondoni, and Temeke districts of Dar es Salaam to sample Ae. aegypti mosquitoes using Biogents Sentinel trap (BGS), Prokopack aspiration, and Gravid Aedes trap (GAT). Collected mosquitoes were pooled in groups of 10 and tested for DENV1–4 serotypes using reverse transcription polymerase chain reaction (RT-qPCR). Blood meal sources were identified using an enzyme-linked immunosorbent assay (ELISA). Of 854 tested pools, only DENV-2 was detected and was found in all three districts: Temeke (3/371 pools), Ilala (1/206 pools), and Kinondoni (1/277 pools). Blood meal analysis showed a strong preference for humans (81%) as well as for mixed blood meals that contained human blood and other hosts (17%). Out of 354 collected hosts seeking Ae. aegypti, 78.5% were captured outdoors and 21.5% indoors. This study confirms the circulation of DENV-2 in Ae. aegypti populations, indicating a potential dengue outbreak risk in Tanzania. This study also demonstrates that xenomonitoring may be feasible in this setting. The mosquitoes’ strong preference for human hosts and predominance in outdoor settings pose challenges for dengue control efforts. Full article

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

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20 pages, 5108 KiB

Open AccessArticle

Case Series of Adverse Pregnancy Outcomes Associated with Oropouche Virus Infection

by Daniele Barbosa de Almeida Medeiros, Juarez Antônio Simões Quaresma, Raimunda do Socorro da Silva Azevedo, Ana Cecilia Ribeiro Cruz, Sandro Patroca da Silva, Arnaldo Jorge Martins Filho, Bruno Tardelli Diniz Nunes, Lucas Rafael Santana Pinheiro, Jorge Rodrigues de Sousa, Jannifer Oliveira Chiang, Lívia Carício Martins, Consuelo Silva Oliveira, Ivy Tissuya Essashika Prazeres, Daniele Feitas Henriques, Camille Ferreira Oliveira, Valéria Lima Carvalho, Clarice Neuenschwander Lins Morais, Bartolomeu Acioli-Santos, Keilla Maria Paze Silva, Diego Arruda Falcão, Mayara Matias de Oliveira Marques Costa, Eduardo Augusto Duque Bezerra, Ana Márcia Drechsler Rio, Neijla Cristina Vieira Cardoso, Juliana Carla Serafim da Silva, Simone Gurmão Ramos, Erika Cavalcante Maranhão, José Lancart de Lima, Pedro Fernando da Costa Vasconcelos, Bruno Issao Matos Ishigami and Lívia Medeiros Neves Casseb Show full author list Hide full author list

Viruses 2025, 17(6), 816; https://doi.org/10.3390/v17060816 - 5 Jun 2025

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Abstract

The Oropouche virus (OROV) is an arbovirus (Peribunyaviridae: Orthobunyavirus) that traditionally causes febrile outbreaks in Latin America’s Amazon region. Previously, OROV was not associated with severe pregnancy outcomes. During the 2022–2024 outbreak in Brazil, OROV expanded geographically, revealing links to adverse pregnancy outcomes. [...] Read more.

The Oropouche virus (OROV) is an arbovirus (Peribunyaviridae: Orthobunyavirus) that traditionally causes febrile outbreaks in Latin America’s Amazon region. Previously, OROV was not associated with severe pregnancy outcomes. During the 2022–2024 outbreak in Brazil, OROV expanded geographically, revealing links to adverse pregnancy outcomes. This study describes six cases with varied fetal outcomes, including miscarriage, antepartum, intrauterine fetal demise (IFD), and normal development, correlating with maternal symptoms but not symptom severity. Vertical transmission was confirmed by detecting OROV through RT-qPCR, ELISA, and immunohistochemistry in fetal tissues. Genome sequencing from an IFD case identified a novel reassortment pattern reported in the 2022–2024 outbreak. Severe encephalomalacia, meningoencephalitis, vascular compromise, and multi-organ damage were evident, underscoring the significant risk OROV poses to fetal development and emphasizing the need for further investigation. Full article

(This article belongs to the Special Issue Oropouche Virus (OROV): An Emerging Peribunyavirus (Bunyavirus))

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15 pages, 1894 KiB

Open AccessArticle

Spatiotemporal Distribution and Host–Vector Dynamics of Japanese Encephalitis Virus

by Qikai Yin, Bin Li, Ruichen Wang, Kai Nie, Shihong Fu, Songtao Xu, Fan Li, Qianqian Cui, Dan Liu, Huanyu Wang and Guodong Liang

Viruses 2025, 17(6), 815; https://doi.org/10.3390/v17060815 - 4 Jun 2025

Viewed by 278

Abstract

Japanese encephalitis (JE), a mosquito-borne viral disease caused by the Japanese encephalitis virus (JEV), remains a significant public health threat in Asia. Although vaccination programs have successfully reduced the incidence of JE, challenges persist in the adult population, and the emergence of rare [...] Read more.

Japanese encephalitis (JE), a mosquito-borne viral disease caused by the Japanese encephalitis virus (JEV), remains a significant public health threat in Asia. Although vaccination programs have successfully reduced the incidence of JE, challenges persist in the adult population, and the emergence of rare JEV genotypes poses additional risks. In this study, a phylogenetic analysis of the whole JEV genome sequence, along with a temporal–spatial analysis of isolates and a host–vector analysis, was used to examine the changes in JEV transmission dynamics before and after 2012. The results revealed persistent differences between the dominant G1 and G3 genotypes, as well as the re-emergence of G4 and G5 genotypes. Although JEV has been detected in non-traditional vectors and atypical mammalian hosts, Culex tritaeniorhynchus and pigs remain the primary vector and amplifying host, respectively. These findings underscore the need to enhance existing JEV genotype surveillance while addressing emerging threats from genotype diversity, host expansion, and geographic spread. Full article

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

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Viruses, Volume 17, Issue 6 (June 2025) – 107 articles

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