Journal of Virology最新文献

{"title":"A multivalent mRNA-lipid nanoparticle vaccine containing eight hemagglutinin antigens elicited broad neutralizing antibody responses and protected against influenza A virus challenge in swine.","authors":"Giovana Ciacci Zanella, Marissa L Vincent, Leo Flores, Ethan K Aljets, Rodrigo C Paiva, Alexey Markin, Blake Inderski, Garima Dwivedi, Drew Weissman, Meghan Wymore Brand, Jefferson J S Santos, Scott E Hensley, Tavis K Anderson, Phillip C Gauger, Amy L Baker","doi":"10.1128/jvi.00848-26","DOIUrl":"https://doi.org/10.1128/jvi.00848-26","url":null,"abstract":"<p><p>The diversity within H1 and H3 subtype influenza A viruses (IAVs) in swine prevents effective vaccine control approaches with inactivated whole-virus vaccines. We addressed the challenge of controlling co-circulating hemagglutinin (HA) clades of swine IAV with the development of a multivalent messenger RNA (mRNA)-lipid nanoparticle (LNP) vaccine expressing eight HA proteins to maximize genetic coverage. We applied a computational approach to select eight HA genes that represented 95% of the observed IAVs detected in the United States between 2022 and 2025. Piglets were vaccinated and boosted intramuscularly with either individual HA mRNA-LNP or an 8-HA multivalent mRNA-LNP. Serum was collected to evaluate systemic antibody levels. Twenty-one days post-boost, pigs were challenged with a field-relevant H1 1A.3.3.3-c3 IAV strain. The 8-HA multivalent mRNA-LNP vaccine induced neutralizing antibodies against all eight antigens, and vaccinees were protected against lung lesions, with lesion scores similar to non-challenged animals. Homologous monovalent vaccination significantly reduced IAV detection in nasal secretions and in the lungs. Heterologous monovalent vaccination was not cross-protective but did not induce vaccine-associated enhanced respiratory disease. We provide evidence that monovalent and multivalent mRNA-LNP influenza vaccines elicited neutralizing antibody responses in pigs and protected against viral challenge. The versatility and capacity for rapidly updating the mRNA-LNP vaccine platform make it an appealing tool to improve animal health and minimize the circulation and diversity of IAV in swine.IMPORTANCEInfluenza A virus (IAV) is an important respiratory pathogen in swine, and zoonotic transmission of swine strains to humans remains a public health risk. Control strategies against IAV in swine herds rely heavily on biosecurity measures and vaccination. However, the antigenic diversity of IAV circulating in swine challenges current vaccination programs, and there is a need for broadly protective vaccines or platforms that can rapidly update components to reflect circulating diversity. mRNA-LNP vaccines have emerged as promising vaccine platforms, offering simultaneous delivery of multiple antigens, rapid development, scalable manufacturing, and potent immunogenicity. In this study, we assessed the immunogenicity and protective capacity of monovalent and multivalent mRNA-LNP vaccines encoding eight representative IAV hemagglutinin (HA) antigens. To our knowledge, this is the first study to objectively select multiple representative endemic swine IAV strains by quantifying genetic diversity within the phylogeny and to apply this selection to rationally design and evaluate a multivalent HA mRNA-based influenza vaccine in the swine model.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0084826"},"PeriodicalIF":4.1,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"H5 influenza virus mRNA-lipid nanoparticle (LNP) vaccination elicits adaptive immune responses in Holstein calves.","authors":"Carine K Souza, Jefferson J S Santos, Paola Boggiatto, Haley Sterle, Bailey Arruda, Mitchell V Palmer, Alessandra Campos, Jiaojiao Liu, Naiqing Ye, Drew Weissmann, Scott E Hensley, Amy L Baker","doi":"10.1128/jvi.01289-26","DOIUrl":"https://doi.org/10.1128/jvi.01289-26","url":null,"abstract":"<p><p>Highly pathogenic avian influenza (HPAI) clade 2.3.4.4b H5N1 circulated widely in lactating dairy cows in the United States following the initial detection in 2024. Due to the critical need for intervention strategies for this outbreak, we evaluated antibody and cellular immune responses of a clade 2.3.4.4b H5 mRNA-LNP vaccine in calves. We found that the H5 mRNA-LNP vaccine induced a robust antibody and CD8⁺ T cell-mediated immune response and conferred protection against clade 2.3.4.4b H5N1 infection.IMPORTANCEIt is important to develop vaccines that limit clade 2.3.4.4b H5N1 infection in cattle. In this study, we found that a new H5 mRNA-lipid nanoparticle vaccine is immunogenic when delivered intramuscularly to male Holstein calves.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0128926"},"PeriodicalIF":4.1,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extensive variation in virus-induced patterns of transposable element transcripts in <i>Drosophila</i>.","authors":"Camille A Mayeux, Chloé Garambois, Anaïs Larue, Julie Delescluse, Marie Fackeure, Vincent Lacroix, Hélène Henri, Natacha Kremer, Rita Rebollo, Séverine Chambeyron, Matthieu Boulesteix, Marie Fablet","doi":"10.1128/jvi.01071-26","DOIUrl":"https://doi.org/10.1128/jvi.01071-26","url":null,"abstract":"<p><p>Transposable elements (TEs) are widespread genomic parasites, whose activity is largely restrained by RNA interference pathways. Some of these pathways also contribute to antiviral immunity, allowing a mechanistic overlap that could generate interactions-or even trade-offs-between TE repression and viral defense. Here, we investigated this interplay by experimentally infecting two strains of <i>Drosophila melanogaster</i> and <i>Drosophila simulans</i> with three distinct viruses: <i>Drosophila</i> X virus (DXV), Flock House virus (FHV), and Invertebrate Iridescent virus 6 (IIV6). Through deep RNA-seq and small RNA-seq analyses, we show that viral infection consistently alters TE transcript abundance, although the direction and magnitude of these changes strongly depend on both the host strain and the virus. In addition, we provide an in-depth characterization of the dynamic TE repertoire that IIV6 carries.IMPORTANCETransposable elements (TEs) are genomic parasites that are found in all genomes. Here, using two strains of <i>Drosophila</i> and three viruses, we show that viral infections consistently affect TE transcript amounts. However, the magnitude and direction of the TE modulation depend on the host strain, the virus, and the tissue. In addition, one of the viruses under study, the Invertebrate Iridescent virus 6 (IIV6), carries TEs on its own, which we characterize as a dynamic repertoire.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0107126"},"PeriodicalIF":4.1,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Powassan virus LB neuroinvasion and lethality are determined by envelope protein domain III residues.","authors":"Marissa R Lindner, Elena E Gorbunova, Marcos Romario Matos de Souza, Grace E Himmler, Hwan Keun Kim, Erich R Mackow","doi":"10.1128/jvi.00963-26","DOIUrl":"10.1128/jvi.00963-26","url":null,"abstract":"<p><p>Powassan viruses (POWVs) are tick-borne orthoflaviviruses that cause lethal encephalitis and long-term neurologic sequelae. POWVs are divided into two lineages that share 86% genetic identity. POWV-LB (Lin I) was isolated from a fatal case of encephalitis, while POWV-LI9 (Lin II) is a tick-derived isolate that causes age-dependent lethality in mice. Domain III of orthoflavivirus envelope proteins (EDIII) directs cell attachment and determines murine neuropathology and lethality. Here, we developed POWV LB reverse genetics, analyzed brains of LB- and recLB mutant-infected mice, and assessed the role of EDIII residues in LB pathogenesis. LB infection of 50-week-old B6 mice focally activated microglia in the midbrain and cerebellum, discrete from and independent of the location of envelope protein in the cerebral cortex, hippocampus, and thalamus. Reverse genetic analysis of LB EDIII residues revealed that mutating D308N only partially reduced LB neuropathology and lethality. However, mutating D308N along with an adjacent EDIII residue, A310T, completely abolished LB-D308N/A310T neuroinvasion and lethality, yet elicited neutralizing antibody responses that protected mice from a lethal WT LB challenge. Signifying a change in neuroinvasion, LB-D308N/A310T failed to activate microglia or yield detectable POWV RNA and antigen in the CNS. Overall, recombinant LB-D308N/A310T mutants fail to induce neurologic symptoms or neuropathology while eliciting a protective immune response. These findings reveal that EDIII residues determine the neuroinvasion and lethality of lineage I POWVs and that genetically modifying EDIII provides a mechanism for POWV attenuation and vaccine development.IMPORTANCEPowassan virus causes lethal encephalitis and long-term neurological sequelae in survivors; however, there are currently no licensed POWV vaccines or therapeutics. POWVs are comprised of two genetic lineages (LB-Lin I and LI9 Lin II) that are derived from discrete ticks and small mammal hosts. Orthoflavivirus envelope proteins determine cell attachment, viral tropism, and neurovirulent spread and lethality in mice. Here, we created a POWV LB reverse genetics system and assessed mutations that determine LB neuroinvasion in 50-week-old mice. Studies reveal novel LB neuropathology with divergent patterns of gliosis and POWV antigen expression within the CNS. Mice subcutaneously infected with an LB-D308N/A310T envelope mutant elicited responses that protect mice from a lethal LB challenge and failed to enter the CNS or cause neurologic symptoms, CNS pathology, or lethality. LB reverse genetics permits defining the determinants of LB neuroinvasion that are required for rational vaccine development.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0096326"},"PeriodicalIF":4.1,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"What a tangled web we weave: how agriculture, a polyphagous insect vector, and rampant recombination drove the emergence, evolution, and economic importance of the geminivirus beet curly top virus in western North America.","authors":"Tomas A Melgarejo, Li-Fang Chen, Mônica A Macedo, Margaret K Cespedes, Thomas Turini, William M Wintermantel, Robert L Gilbertson","doi":"10.1128/jvi.00840-26","DOIUrl":"https://doi.org/10.1128/jvi.00840-26","url":null,"abstract":"<p><p>Curly top disease (CTD) of sugar beet is characterized by leaf curling and stunted growth. Historic CTD emerged independently in western North America (~1900), South America (~1925), and the Middle East (~1955), following intensive cultivation of this Old World crop. In these regions, CTD is caused by genetically distinct monopartite geminiviruses transmitted by different leafhopper species. In North America, CTD is caused by 11 strains of beet curly top virus (BCTV) and transmitted by the beet leafhopper (BLH, <i>Circulifer tenellus</i>). Here, the emergence and evolution of BCTV and the role of agriculture were investigated using 133 genome sequences of isolates collected from multiple crops and locations over nearly a century, including 32 recent sequences from New World (NW) crops in California. New strains were not identified, and all isolates are recombinant and have four conserved breakpoints. Recombination-aware evolutionary analyses estimated BCTV emerged ~750 years ago, likely from a progenitor infecting uncultivated NW plants. Diversification was associated with the domestication of NW crops, especially pepper; the introduction of sugar beet; and the emergence of mild- and severe-type sugar beet strains. Overgrazing of grasses in foothills allowed proliferation of weed reservoirs of BCTV and BLH. Isolates recently collected from NW crops and weeds were mostly mild-type strains, revealing a strain shift. The C4 effector protein of mild-type strains is nearly completely disordered (99%) compared with 44% for severe-type strains, suggesting a role in adaptive evolution. Thus, the evolution of BCTV and CTD biology were driven by agricultural practices, genetic flexibility of BCTV, and the polyphagous BLH vector.IMPORTANCEThis study revealed how the emergence and evolution of beet curly top virus (BCTV) and curly top disease in the western United States beginning ~ 1900 was facilitated by agriculture. Results of historic and molecular genetic studies showed BCTV emerged and diversified during the domestication of New World (NW) crops and subsequently after the introduction and intensification of Old World sugar beet. Invasive dicot weeds colonizing overgrazed foothill areas provided reservoirs for BCTV and the beet leafhopper vector. The long evolutionary history of BCTV, mediated by recombination and genetic drift, resulted in strains adapted to sugar beet (severe-type) and NW crops (mild-type). Following reduced sugar beet cultivation in California, mild-type strains underwent population expansion and became predominant in NW crops, facilitated by a highly disordered C4 effector protein. Thus, the genetic flexibility of BCTV, the polyphagous vector, and changing agricultural practices drove the emergence and persistence of this economically important plant disease.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0084026"},"PeriodicalIF":4.1,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Humoral response against Epstein-Barr virus follows a strain-specific and HIV-driven pattern.","authors":"Eric D Eymard, Dicle Yalcin, Owen Ngalamika, Salum J Lidenge, John T West, Charles Wood","doi":"10.1128/jvi.01043-26","DOIUrl":"https://doi.org/10.1128/jvi.01043-26","url":null,"abstract":"<p><p>Epstein-Barr virus (EBV) is a ubiquitous human gammaherpesvirus causally linked to several malignancies, including lymphomas and solid tumors. Despite its high global prevalence, a comprehensive profile of humoral responses to EBV is yet to be described. Moreover, how HIV-1 co-infection influences this response can reveal new insights into how cancer risk increases in people with HIV-1 (PWH). Here, we employed phage immunoprecipitation and sequencing (PhIP-Seq) using the VirScan phage-display library to map antibody responses against the EBV proteome in 115 adults from sub-Saharan Africa, with and without HIV-1 co-infection (43 HIV-positive and 72 HIV-negative) at peptide-level resolution. We identified EBNA1, EBNA2, EBNA3B, and the viral capsid antigen protein BFRF3 as the most immunodominant EBV proteins. Differential antibody reactivities between EBV Type 1 and Type 2 were observed against EBNA2, with increased antibody recognition near the C-terminal transactivation domain (C-TAD) observed for Type 1. A specific region of EBNA1 containing the nuclear localization sequence (NLS) was the most frequently targeted epitope of the EBV proteome. Our comprehensive and high-resolution analysis identified several immunodominant EBV proteins that are targeted by most individuals regardless of HIV-1 status. HIV-1 co-infected individuals (PWH) had increased antibody recognition against most EBV proteins compared to HIV-uninfected individuals, but the magnitudes of those responses varied across the proteome. Overall, our findings suggest that HIV-1 co-infection alters both the breadth and magnitude of anti-EBV responses, potentially reflecting increased viral reactivation and HIV-driven mechanisms of immunosuppression that may impact the magnitude of antibody responses in EBV.IMPORTANCEThis study employs the first comprehensive high-resolution antibody profiling against Epstein-Barr virus (EBV) among healthy adults and people with HIV-1 (PWH). Our results indicated that HIV-1 has a considerable influence on the anti-EBV repertoire that may provide further evidence of how HIV-1 significantly increases the risk of EBV-associated malignancies such as lymphoma. We showed evidence that HIV-1 co-infection leads to higher exposure to viral antigens, likely due to viral reactivation, reflected by a higher percentage of patients with antibodies reactive to the majority of EBV proteins when compared to people without HIV-1. Since PWH are known to be more susceptible to EBV-associated cancers, whether these changes in humoral immune response can be used as prognostic biomarkers for cancer risks should be further investigated with longitudinal studies.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0104326"},"PeriodicalIF":4.1,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pre-existing cross-subtype serological responses against H5Nx in health care workers.","authors":"Katrina Dionne, Étienne Bélanger, Mehdi Benlarbi, Guillaume Beaudoin-Bussières, Claudia Santos Saenz, Shilei Ding, Catherine Bourassa, Halima Medjahed, Morgan Jennings, Geneviève Laroche, Julie Carbonneau, Elie Haddad, Madeleine Durand, Guy Boivin, Marceline Côté, Andrés Finzi","doi":"10.1128/jvi.01310-26","DOIUrl":"https://doi.org/10.1128/jvi.01310-26","url":null,"abstract":"<p><p>A rise in cases of highly pathogenic avian influenza A (H5N1) clade 2.3.4.4b in humans has been reported since 2023. Although influenza seasonal vaccination (H1N1/H3N2) was shown to be effective against cases of reinfection with endemic influenza A viruses (IAVs), its capacity to elicit cross-reactive antibodies against (H5N1) remains unclear. Here, we measured vaccine-elicited antibody responses against seasonal (H1N1/H3N2) and various avian subtypes A (H5Nx) using plasma samples from the CRCHUM Health Care Workers cohort in Montreal, Canada, during the 2024 influenza seasonal vaccination. The capacity of their plasma to recognize hemagglutinin (HA) and neuraminidase (NA) antigens from ten influenza strains was measured. Their neutralizing activity, as well as their capacity to mediate antibody-dependent cellular cytotoxicity (ADCC) against cells stably expressing HA and NA, was measured. Overall, seasonal vaccination against H1N1/H3N2 elicited antibodies able to recognize several HA and NA, and in some individuals, this translated to increased neutralization and ADCC activity, including against H5Nx. This study provides insightful information on how vaccination shapes cross-reactive antibody responses against avian H5Nx.</p><p><strong>Importance: </strong>Influenza A viruses (IAVs) are endemic in the human population and responsible for hundreds of thousands of deaths every year, occasionally leading to influenza pandemics. Since 2023, there has been a rise in avian IAV infections in humans, with some deaths reported, mostly related to the H5N1 subtype clade 2.3.4.4b. Seasonal vaccines against IAVs are effective, but their efficacy against avian IAVs is not well known. Here, following influenza seasonal vaccination in a cohort of adults, we report highly heterogeneous serological responses, possibly due to pre-existing immunity and HA sequence similarity. These findings provide insight into the breadth of pre-existing and vaccine-induced immunity against H5 influenza viruses and may inform the development of vaccination strategies aimed at providing broader protection against emerging influenza viruses.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0131026"},"PeriodicalIF":4.1,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing tretinoin, a vitamin A derivative, against Chikungunya virus infection.","authors":"Soumyajit Ghosh, Chandan Mahish, Archana Mahapatra, Tathagata Mukherjee, Pratima Kumari, Bijita Bhowmick, Saikat De, Udvas Ghorai, Rajshree Rajmohan Jena, Seema Pradhan, Subhasis Chattopadhyay, Soma Chattopadhyay","doi":"10.1128/jvi.00558-26","DOIUrl":"https://doi.org/10.1128/jvi.00558-26","url":null,"abstract":"<p><p>Chikungunya virus (CHIKV) has reemerged as a global pathogen causing serious public health threat, particularly due to the absence of specific antivirals. Retinoids, vitamin A derivatives, have demonstrated antiviral potential against different viral infections, yet their efficacy against alphaviruses has never been investigated. In this study, tretinoin (TR), or all-trans retinoic acid (ATRA), was evaluated for its anti-CHIKV activity using <i>in vitro</i>, <i>in vivo</i>, and <i>ex vivo</i> models. TR abrogated CHIKV infection efficiently in Vero and C2C12 cells, with a marked reduction (>90%) in viral RNA, proteins, and progeny formation. The IC₅₀ of TR against CHIKV was estimated to be 20.05 µM and 19.71 µM in Vero and C2C12 cells, respectively. Additionally, TR showed remarkable virucidal activity and effective inhibition during entry, as well as in the early stages of post-CHIKV infection. Next, the global transcriptome profile demonstrated that the \"signaling by retinoic acid\" pathway was significantly enriched after CHIKV infection, and retinoic acid receptors (RARs), specifically RAR-β, are the key mediators for the anti-CHIKV effect of TR. Further, the drug alters phosphorylated mitogen-activated protein kinases (MAPKs), NF-κB, and proinflammatory cytokines during CHIKV infection in RAW 264.7 cells. Interestingly, TR protected C57BL/6 mice from CHIKV challenge by diminishing viral burden, leading to reduced clinical scores and better survival. Similar observations were also noticed in the <i>ex vivo</i> models of CHIKV-infected primary human skeletal muscle myoblasts (HSMMs). In conclusion, this work demonstrated the repurposing potential of TR against CHIKV infection for the first time, encouraging its clinical validation toward future therapeutics.</p><p><strong>Importance: </strong>Chikungunya virus (CHIKV) is an arbovirus causing Chikungunya fever (CHIKF), leading to debilitating arthralgia and myalgia. The unavailability of licensed antivirals against CHIKV encourages extensive research to find a therapeutic cure. Retinoids, the derivatives of vitamin A, have been repurposed as antiviral agents against a broad range of viruses; however, their potency against alphaviruses remains unexplored. Accordingly, tretinoin (TR), also known as all-trans retinoic acid (ATRA), was validated for anti-CHIKV efficacy in this investigation. Significant perturbations of CHIKV titer, RNA, and protein levels were observed in the presence of TR following infection, and its antiviral effect was mediated through RAR-β. Moreover, the anti-CHIKV potential of TR was evaluated in the mouse model and primary human skeletal muscle myoblasts, indicating strong preclinical efficacy. Finally, this is the first study to report the antiviral property of TR against CHIKV infection using <i>in vitro</i>, <i>in vivo</i>, and <i>ex vivo</i> approaches, suggesting its repurposing potential.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0055826"},"PeriodicalIF":4.1,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Infection and transmission dynamics of bovine and human influenza A H5N1 viruses in mouse and hamster models.","authors":"Mohammed Nooruzzaman, David W Buchholz, Ruchi Rani, Pablo Sebastian Britto de Oliveira, Richard A Adeleke, Chen Feng, Nicholas Vazquez, Elena A Demeter, Hector C Aguilar, Diego G Diel","doi":"10.1128/jvi.01044-26","DOIUrl":"https://doi.org/10.1128/jvi.01044-26","url":null,"abstract":"<p><p>Here we investigated the pathogenesis and contact transmission of bovine- and human-derived highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b genotype B3.13 viruses in mammalian models. Using reverse genetics, we rescued three naturally occurring viruses, rTX2/24 (bovine-derived), rTexas/37, and rMichigan/90 (both human-derived), and compared their infection dynamics, replication, and pathogenicity with the wild-type bovine TX2/24 strain <i>in vitro</i> and <i>in vivo</i>. All four viruses demonstrated comparable replication kinetics in four mammalian cell lines. However, the rMichigan/90 strain exhibited smaller plaques in bovine and human cells. <i>In vivo</i> studies showed that mice infected with any of the viruses succumbed to infection within 4-5 days; however, mice infected with the rMichigan/90 virus exhibited slightly lower viral replication and shedding compared with the other strains. The hamster model showed a milder infection phenotype than mice in which all viruses induced body weight loss and oral shedding, with robust virus replication observed in tissues, but the rMichigan/90 virus presented reduced replication and shedding. Contact transmission studies in hamsters revealed limited transmissibility for these viruses, with only one out of four animals inoculated with the rMichigan/90 virus transmitting it to a naïve contact. These findings indicate that both bovine- and human-derived H5N1 genotype B3.13 viruses present high pathogenicity in rodent models, though the overall respiratory transmissibility remains low in the hamster model.IMPORTANCEInfluenza A H5N1 virus spilled over from wild birds into dairy cattle in the United States in 2024. Since then, an increased number of human infections-with at least 71 confirmed cases-have been confirmed. In the present study, we evaluated and compared the pathogenicity and transmissibility of a bovine and two human H5N1 viruses of the genotype B3.13. Our results show that while all viruses are pathogenic in mouse and hamster models, the bovine isolate TX2/24 presents a broader tissue tropism than the human-derived viruses. Contact transmission studies revealed a limited ability of these viruses to transmit in the hamster contact transmission model. These findings highlight the high pathogenicity of H5N1 viruses in mammals and demonstrate that their respiratory transmissibility potential remains low in the hamster model.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0104426"},"PeriodicalIF":4.1,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endogenous anti-Ebola virus GP_1,2 antibodies interfere with detection of secreted glycoprotein in the blood of EVD patients.","authors":"Patrick T Tshita, Aurélie Ploquin, John Misasi, Bobo N Bazola, Samuel M Shamamba, Hadar Marcus, Ange Y Mubiala, Francis M Ntumba, Saidou Milua, Courtney Tucker, Eddy Kinganda-Lusamaki, Emmanuel Lokilo, Raphael Lumbembe, Aziza Amuri, Naomie Bayoka, Anthony Suangi, Christian M Kahusu, Ilombe Myriam Mbilizi, Olivier Tshiani-Mbaya, Denis K Kandolo, Placide Mbala-Kingebeni, Sabue Mulangu, Jean-Jacques Muyembe-Tamfum, Nancy J Sullivan, Dacquin M Kasumba","doi":"10.1128/jvi.01414-26","DOIUrl":"https://doi.org/10.1128/jvi.01414-26","url":null,"abstract":"<p><p>Ebola disease (EBOD) is a highly infectious disease with severe hemorrhagic symptoms. It is caused by orthoebolaviruses<i>,</i> which include the Ebola virus (<i>Orthoebolavirus zairense</i>) (EBOV) causing Ebola virus disease (EVD), the most lethal EBOD to humans. Through co-transcriptional polymerase stuttering and subsequent proteolytic processing, its <i>GP</i> gene produces multiple protein products, including secreted glycoprotein (sGP) and structural membrane-associated trimeric GP_1,2. Although sGP is known to circulate in the blood, its physiological significance in disease pathology remains speculative. We quantified sGP using enzyme-linked immunosorbent assay (ELISA) in 36 acute human EVD cases from the 10th and 11th EVD outbreaks in the Democratic Republic of the Congo (DRC) using single-time-point biobanked samples. We detected and quantified sGP in four patients with strong <i>GP</i> gene transcription (GP Ct < 25), as evidence of viral replication, but with no endogenous anti-EBOV GP_1,2 IgG. However, sGP was not quantified in patients with lower GP transcription (Ct > 25), regardless of their anti-EBOV GP_1,2 IgG results. While two patients, MAM179 and MAM271, had notably strong GP transcription (Ct < 25), their high amounts of endogenous anti-EBOV GP_1,2 IgG might have interfered with detection by the assay detection antibody, a human anti-EBOV GP_1,2/sGP IgG. Furthermore, the addition of sera containing anti-EBOV GP_1,2 IgG reduced the binding between sGP and anti-EBOV GP_1,2/sGP used as detection antibodies. This suggested that the level of sGP in circulation is strongly linked to the intensity of <i>GP</i> transcription. Additionally, circulating sGP in this context would form complexes with anti-GP_1,2 antibodies, hence hindering additional antibody binding for detection.IMPORTANCEInsight into the mechanism of immune function by the Ebola virus secreted glycoprotein (sGP) in humans is essential for better understanding viral pathogenesis, immune protection, and immune evasion strategies. Research utilizing samples from patients who are infected with or have survived infection with the Ebola virus offers an unparalleled opportunity to determine the immunological significance of sGP. This research evaluates, in acutely infected patients from Ebola virus disease outbreaks, the role of EBOV sGP in modulating antibody responses directed against viral entry glycoprotein. By elucidating how sGP influences antibody-mediated immunity, the study advances our understanding of a conserved immune-evasion mechanism shared across all orthoebolaviruses. These investigations are valuable resources for designing more efficacious vaccines, therapies, and biomarkers for monitoring Ebola virus diseases.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0141426"},"PeriodicalIF":4.1,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}