Journal of Virology最新文献

{"title":"Human long noncoding RNA <i>VILMIR</i> is induced by major respiratory viral infections and modulates the host interferon response.","authors":"Kristen John, Ian Huntress, Ethan Smith, Hsuan Chou, Tammy S Tollison, Sergio Covarrubias, Elisa Crisci, Susan Carpenter, Xinxia Peng","doi":"10.1128/jvi.00141-25","DOIUrl":"10.1128/jvi.00141-25","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Long noncoding RNAs (lncRNAs) are a newer class of noncoding transcripts identified as key regulators of biological processes. Here, we aimed to identify novel lncRNA targets that play critical roles in major human respiratory viral infections by systematically mining large-scale transcriptomic data sets. Using bulk RNA-sequencing (RNA-seq) analysis, we identified a previously uncharacterized lncRNA, named virus-inducible lncRNA modulator of interferon response (&lt;i&gt;VILMIR&lt;/i&gt;), that was consistently upregulated after &lt;i&gt;in vitro&lt;/i&gt; influenza infection across multiple human epithelial cell lines and influenza A virus subtypes. &lt;i&gt;VILMIR&lt;/i&gt; was also upregulated after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and respiratory syncytial virus (RSV) infections &lt;i&gt;in vitro&lt;/i&gt;. We experimentally confirmed the response of &lt;i&gt;VILMIR&lt;/i&gt; to influenza infection and interferon-beta (IFN-β) treatment in the A549 human epithelial cell line and found the expression of &lt;i&gt;VILMIR&lt;/i&gt; was robustly induced by IFN-β treatment in a dose- and time-specific manner. Single-cell RNA-seq analysis of bronchoalveolar lavage fluid samples from coronavirus disease 2019 (COVID-19) patients uncovered that &lt;i&gt;VILMIR&lt;/i&gt; was upregulated across various cell types, including at least five immune cells. The upregulation of &lt;i&gt;VILMIR&lt;/i&gt; in immune cells was further confirmed in the human T cell and monocyte cell lines, SUP-T1 and THP-1, after IFN-β treatment. Finally, we found that knockdown of &lt;i&gt;VILMIR&lt;/i&gt; expression reduced the magnitude of host transcriptional responses to both IFN-β treatment and influenza A virus infection in A549 cells. Together, our results show that &lt;i&gt;VILMIR&lt;/i&gt; is a novel interferon-stimulated gene (ISG) that regulates the host interferon response and may be a potential therapeutic target for human respiratory viral infections upon further mechanistic investigation.IMPORTANCEIdentifying host factors that regulate the immune response to human respiratory viral infection is critical to developing new therapeutics. Human long noncoding RNAs (lncRNAs) have been found to play key regulatory roles during biological processes; however, the majority of lncRNA functions within the host antiviral response remain unknown. In this study, we identified that a previously uncharacterized lncRNA, virus-inducible lncRNA modulator of interferon response (&lt;i&gt;VILMIR&lt;/i&gt;), is upregulated after major respiratory viral infections including influenza, severe acute respiratory syndrome coronavirus 2, and respiratory syncytial virus. We demonstrated that &lt;i&gt;VILMIR&lt;/i&gt; is an interferon-stimulated gene that is upregulated after interferon-beta (IFN-β) in several human cell types. We also found that knockdown of &lt;i&gt;VILMIR&lt;/i&gt; reduced the magnitude of host transcriptional responses to IFN-β treatment and influenza A infection in human epithelial cells. Our results reveal that &lt;i&gt;VILMIR&lt;/i&gt; regulates the host interferon response and may present a new therapeut","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0014125"},"PeriodicalIF":4.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700874","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":"HSV-1 infection induces a downstream shift of the +1 nucleosome.","authors":"Elena Weiß, Adam W Whisnant, Thomas Hennig, Lara Djakovic, Lars Dölken, Caroline C Friedel","doi":"10.1128/jvi.02086-24","DOIUrl":"https://doi.org/10.1128/jvi.02086-24","url":null,"abstract":"<p><p>Herpes simplex virus 1 (HSV-1) infection induces a loss of host transcriptional activity and widespread disruption of host transcription termination, which leads to an induction of open chromatin downstream of genes. In this study, we show that lytic HSV-1 infection also leads to an extension of chromatin accessibility at promoters into downstream regions. This is most prominent for highly expressed genes and independent of the HSV-1 proteins ICP0, ICP22, ICP27, and <i>vhs</i>. ChIPmentation of the noncanonical histone variant H2A.Z, which is strongly enriched at +1 and -1 nucleosomes, indicated that these chromatin accessibility changes are linked to a downstream shift of +1 nucleosomes. In yeast, downstream shifts of +1 nucleosomes are induced by RNA polymerase II (Pol II) degradation. Accordingly, irreversible depletion of Pol II from genes in human cells using α-amanitin altered +1 nucleosome positioning similar to lytic HSV-1 infection. Consequently, treatment with phosphonoacetic acid and knockout of ICP4, which both prevent viral DNA replication and alleviate the loss of Pol II from host genes, largely abolished the downstream extension of accessible chromatin in HSV-1 infection. In the absence of viral genomes, doxycycline-induced expression of ICP27, which redirects Pol II from gene bodies into intergenic regions by disrupting transcription termination, induced an attenuated effect that was further enhanced by co-expression of ICP22. In summary, our study provides strong evidence that HSV-1-induced depletion of Pol II from the host genome leads to a downstream shift of +1 nucleosomes at host promoters.IMPORTANCELytic herpes simplex virus 1 (HSV-1) infection leads to a profound host transcription shutoff. Loss of RNA polymerase II (Pol II) in yeast has previously been shown to relax +1 nucleosome positioning to more thermodynamically favorable sites downstream of transcription start sites. Here, we show that a similar phenomenon is likely at play in lytic HSV-1 infection. Sequencing of accessible chromatin revealed a widening of nucleosome-free regions at host promoters into downstream regions. By mapping genome-wide positions of the noncanonical histone variant H2A.Z enriched at +1 and -1 nucleosomes, we demonstrate a downstream shift of +1 nucleosomes for most cellular genes in lytic HSV-1 infection. As chemical depletion of Pol II from genes also leads to a downstream shift of +1 nucleosomes in human cells, changes in chromatin architecture at promoters in HSV-1 infection are likely a consequence of HSV-1-induced loss of Pol II activity from the host genome.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0208624"},"PeriodicalIF":4.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700868","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":"<i>Parechovirus</i>: neglected for too long?","authors":"Fahmida Alam, You Li, Matthew R Vogt","doi":"10.1128/jvi.01846-24","DOIUrl":"10.1128/jvi.01846-24","url":null,"abstract":"<p><p>Parechoviruses are non-enveloped, positive-sense, single-stranded RNA viruses that have been isolated from multiple vertebrate species. Infection with these etiologic agents of typically mild childhood respiratory and gastrointestinal illness in humans is nearly universal, and a subset of infected neonates and infants develop severe neurologic diseases. Rodent parechoviruses cause myocarditis, encephalitis, and perinatal death in multiple rodent species. The key steps of the viral life cycle, clinical characteristics, and global burden of these viruses are not well characterized yet, particularly for nonhuman parechoviruses. Here, we review the history of human and nonhuman parechovirus isolation, global seroprevalence and distribution, viral biology, and evolution, considering these factors might contribute to host specificity, virulence, tissue tropism, pathogenesis, host immunity, and population dynamics.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0184624"},"PeriodicalIF":4.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700816","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":"Detection of antibodies against influenza A viruses in cattle.","authors":"Yuekun Lang, Lei Shi, Sawrab Roy, Dipali Gupta, Chao Dai, Muhammad Afnan Khalid, Michael Z Zhang, Shuping Zhang, Xiu-Feng Wan, Richard Webby, Wenjun Ma","doi":"10.1128/jvi.02138-24","DOIUrl":"https://doi.org/10.1128/jvi.02138-24","url":null,"abstract":"<p><p>Unexpected outbreaks caused by the H5N1 highly pathogenic avian influenza virus (HPAIV) in dairy cows in the United States (US) have raised significant veterinary and public health concerns. When and how the H5N1 HPAIV was introduced into dairy cows and the broader epidemiology of influenza A virus (IAV) infections in cattle in the US remain unclear. Herein, we performed a retrospective study to screen more than 1,700 cattle serum samples collected from different bovine breeds in the US from January 2023 to May 2024 using an enzyme-linked immunosorbent assay (ELISA) targeting the nucleoprotein (NP) to detect IAV infections, and the positive samples were further tested by hemagglutination inhibition (HI) assay. Results showed that 586 of 1,724 samples (33.99%) from 15 US states were seropositive by the NP ELISA assay, including 78 samples collected in 2024 and 508 samples collected in 2023. Moreover, the HI assay revealed that 45 of these ELISA-positive samples were positive to human seasonal H1N1 and H3N2 and swine H3N2 and H1N2 viruses, and some were positive to two or three tested IAVs. Surprisingly, none of these ELISA-positive samples were HI positive for the circulating bovine H5N1 strain. Our results demonstrate that IAVs other than H5N1 can infect cattle, infections are not limited to dairy cows, and that bovine infections with swine and human IAVs have occurred prior to the H5N1 outbreaks. All results highlight the value in monitoring IAV epidemiology in cattle, as the viruses might adapt to cattle and/or reassort with the currently circulating H5N1 HPAIV, increasing risk to humans.IMPORTANCEInfluenza A virus (IAV) is an important zoonotic pathogen that can infect different species. Although cattle were not historically considered vulnerable to IAV infections, an unexpected outbreak caused by H5N1 highly pathogenic avian influenza virus in dairy cows in the United States (US) in early 2024 has raised significant concerns. When and how the virus was introduced into dairy cows and the wider impact of IAV infections in cattle in the US remain unclear. Our retrospective serological screen provided evidence of human and swine H1 and H3 IAV infections in different cattle breeds in addition to dairy cows, although no H5N1 infection was detected. Our results underline the necessity to monitor IAV epidemiology in cattle, as reassortment of IAVs from different species may occur in cattle, generating novel viruses that pose threats to public and animal health.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0213824"},"PeriodicalIF":4.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700864","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":"SARS-CoV-2 neutralizing antibody specificities differ dramatically between recently infected infants and immune-imprinted individuals.","authors":"Bernadeta Dadonaite, Allison R Burrell, Jenni Logue, Helen Y Chu, Daniel C Payne, David B Haslam, Mary A Staat, Jesse D Bloom","doi":"10.1128/jvi.00109-25","DOIUrl":"10.1128/jvi.00109-25","url":null,"abstract":"<p><p>The immune response to viral infection is shaped by past exposures to related virus strains, a phenomenon known as imprinting. For severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), much of the population has been imprinted by a viral spike from an early strain, either through vaccination or infection during the early stages of the COVID-19 pandemic. As a consequence of this imprinting, infection with more recent SARS-CoV-2 strains primarily boosts cross-reactive antibodies elicited by the imprinting strain. Here we compare the neutralizing antibody specificities of imprinted individuals versus infants infected with a recent strain. Specifically, we use pseudovirus-based deep mutational scanning to measure how spike mutations affect neutralization by the serum antibodies of adults and children imprinted by the original vaccine versus infants with a primary infection by an XBB* variant. While the serum neutralizing activity of the imprinted individuals primarily targets the spike receptor-binding domain (RBD), the serum neutralizing activity of infants infected with only XBB* mostly targets the spike N-terminal domain. In these infants, secondary exposure to the XBB* spike via vaccination shifts more of the neutralizing activity toward the RBD, although the specific RBD sites targeted are different from imprinted adults. The dramatic differences in neutralization specificities among individuals with different exposure histories likely impact SARS-CoV-2 evolution.IMPORTANCEWe show that a person's exposure history to different SARS-CoV-2 strains strongly affects which regions on the viral spike that their neutralizing antibodies target. In particular, infants who have just been infected once with a recent viral strain make neutralizing antibodies that target different regions of the viral spike than adults or children who have been exposed to both older and more recent strains. This person-to-person heterogeneity means that the same viral mutation can have different impacts on the antibody immunity of different people.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0010925"},"PeriodicalIF":4.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700893","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":"CD4+ T cells facilitate replication of primary HIV-1 strains in macrophages and formation of macrophage internal virus-containing compartments.","authors":"Sabina Victoria, Johanna Leyens, Lea Marie Meckes, Georgios Vavouras Syrigos, Gabriela Turk, Michael Schindler","doi":"10.1128/jvi.00182-25","DOIUrl":"https://doi.org/10.1128/jvi.00182-25","url":null,"abstract":"<p><p>HIV-1 replication in macrophages is highly variable with internal virus accumulation in so-called virus-containing compartments (VCCs). VCCs represent a reservoir that is shielded from the antiviral immune response. VCC formation has been studied in lab-adapted HIV-1, but it has not been investigated whether primary HIV-1 strains induce VCCs. Furthermore, although macrophages transmit HIV-1 from VCCs to CD4+ T cells, the effect of T cells on VCCs is unknown. We analyzed the ability of primary and lab-adapted HIV-1 to replicate in macrophages, the effect of non-infected CD4+ T cell coculture, and VCC formation. All HIV-1 strains replicated in CD4+ T cells, whereas only lab-adapted HIV-1 replicated efficiently in macrophage monocultures. Coculture with non-infected CD4+ T cells enhanced the replication of primary HIV-1 in macrophages, a process associated with increased VCC formation and dependent on direct cell-to-cell contact. Broadly neutralizing antibodies differentially affected CD4+ T cell-mediated enhancement of HIV-1 replication in macrophages. CD4 antibody treatment of macrophages phenocopied the infection-promoting effect of CD4+ T cell coculture. In conclusion, non-infected CD4+ T cells facilitate primary HIV-1 replication in macrophages, and the induction of VCCs appears to be a proxy for this phenotype. VCC formation and HIV-1 replication in macrophages are promoted by non-infected CD4+ T cells in a CD4- and GP120-dependent manner. Our findings highlight the critical role of T cell-macrophage interaction in HIV-1 replication dynamics and VCC formation and call for strategies to interfere with VCCs in order to target the HIV-1 reservoir in macrophages.IMPORTANCEHere, we focus on the intimate interplay between HIV-1-infected macrophages and CD4+ T cells. Specifically, we analyzed whether primary HIV-1 strains induce virus-containing compartments (VCCs) within macrophages, which are thought to serve as viral sanctuaries and macrophage reservoirs. Notably, primary HIV-1 strains were unable to replicate in macrophages and induce VCCs unless they were cocultured with non-infected CD4+ T cells, leading to enhanced VCC formation and viral replication. This suggests an essential role for non-infected CD4+ T cells in facilitating primary HIV-1 replication in macrophages. Our data highlight the importance of not only addressing the latent HIV-1 T cell reservoir but also targeting VCC formation in macrophages to achieve the ultimate goal of functional HIV-1 cure.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0018225"},"PeriodicalIF":4.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700860","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":"Transmission of bovine H5N1 virus in a hamster model.","authors":"Kiyoko Iwatsuki-Horimoto, Ryuta Uraki, Mutsumi Ito, Tong Wang, Lizheng Guan, Peter Halfmann, Amie Eisfeld, Gabriele Neumann, Seiya Yamayoshi, Yoshihiro Kawaoka","doi":"10.1128/jvi.00147-25","DOIUrl":"https://doi.org/10.1128/jvi.00147-25","url":null,"abstract":"","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0014725"},"PeriodicalIF":4.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700932","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":"SARS-CoV-2 cellular coinfection is limited by superinfection exclusion.","authors":"Anna Sims, Daniel J Weir, Sarah J Cole, Edward Hutchinson","doi":"10.1128/jvi.02077-24","DOIUrl":"https://doi.org/10.1128/jvi.02077-24","url":null,"abstract":"<p><p>The coinfection of individual cells is a requirement for exchange between two or more virus genomes, which is a major mechanism driving virus evolution. Coinfection is restricted by a mechanism known as superinfection exclusion (SIE), which prohibits the infection of a previously infected cell by a related virus after a period of time. SIE regulates coinfection for many different viruses, but its relevance to the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was unknown. In this study, we investigated this using a pair of SARS-CoV-2 variant viruses encoding distinct fluorescent reporter proteins. We show for the first time that SARS-CoV-2 coinfection of individual cells is limited temporally by SIE. We defined the kinetics of the onset of SIE for SARS-CoV-2 in this system, showing that the potential for coinfection starts to diminish within the first hour of primary infection and then falls exponentially as the time between the two infection events is increased. We then asked how these kinetics would affect the potential for coinfection with viruses during a spreading infection. We used plaque assays to model the localized spread of SARS-CoV-2 observed in infected tissue and showed that the kinetics of SIE restrict coinfection-and therefore sites of possible genetic exchange-to a small interface of infected cells between spreading viral infections. This indicates that SIE, by reducing the likelihood of coinfection of cells, likely reduces the opportunities for genetic exchange between different strains of SARS-CoV-2 and therefore is an underappreciated factor in shaping SARS-CoV-2 evolution.</p><p><strong>Importance: </strong>Since SARS-CoV-2 first emerged in 2019, it has continued to evolve, occasionally generating variants of concern. One of the ways that SARS-CoV-2 can evolve is through recombination, where genetic information is swapped between different genomes. Recombination requires the coinfection of cells; therefore, factors impacting coinfection are likely to influence SARS-CoV-2 evolution. Coinfection is restricted by SIE, a phenomenon whereby a previously infected cell becomes increasingly resistant to subsequent infection. Here we report that SIE is activated following SARS-CoV-2 infection and reduces the likelihood of coinfection exponentially following primary infection. Furthermore, we show that SIE prevents coinfection of cells at the boundary between two expanding areas of infection, the scenario most likely to lead to recombination between different SARS-CoV-2 lineages. Our work suggests that SIE reduces the likelihood of recombination between SARS-CoV-2 genomes and therefore likely shapes SARS-CoV-2 evolution.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0207724"},"PeriodicalIF":4.0,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674120","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":"Efficacy of parainfluenza virus 5 (PIV5)-vectored intranasal COVID-19 vaccine as a single dose primer and booster against SARS-CoV-2 variants.","authors":"Ashley C Beavis, Zhuo Li, Kelsey Briggs, María Cristina Gingerich, Elizabeth R Wrobel, Maria Najera, Dong An, Nichole Orr-Burks, Jackelyn Murray, Preetish Patil, Jiachen Huang, Jarrod Mousa, Linhui Hao, Tien-Ying Hsiang, Michael Gale, Stephen B Harvey, S Mark Tompkins, Robert Jeffrey Hogan, Eric R Lafontaine, Hong Jin, Biao He","doi":"10.1128/jvi.01989-24","DOIUrl":"10.1128/jvi.01989-24","url":null,"abstract":"<p><p>Immunization with COVID-19 vaccines has greatly reduced COVID-19-related deaths and hospitalizations from SARS-CoV-2 infection, but waning immunity and the emergence of variants capable of immune escape indicate the need for annual vaccine updates or development of different SARS-CoV-2 vaccine platforms. Parainfluenza virus 5 (PIV5)-vectored intranasal COVID-19 vaccine with the ancestral spike (S) protein (CVXGA1) has been shown to be a promising next-generation COVID-19 vaccine preclinically and is currently being evaluated in humans. This work investigates the immunogenicity and efficacy of CVXGA1 and other PIV5-vectored vaccine candidates expressing additional SARS-CoV-2 nucleoprotein (N) antigen or SARS-CoV-2 variant S proteins of beta, delta, gamma, and omicron variants against homologous and heterologous challenges in hamsters. A single intranasal dose of CVXGA1 induces neutralizing antibodies (nAbs) against SARS-CoV-2 WA1 (ancestral), delta variant, and omicron variant and protects against both homologous and heterologous virus challenges. Compared to mRNA COVID-19 vaccine, neutralizing antibody titers induced by CVXGA1 were well maintained over time. When administered as a booster following two doses of an mRNA COVID-19 vaccine, PIV5-vectored vaccines expressing the S protein from WA1 (CVXGA1), delta, or omicron variants generate higher levels of cross-reactive nAbs than three doses of mRNA vaccine. Our data indicate that an intranasal PIV5-vectored COVID-19 vaccine can serve as a booster vaccine against emerging variants.</p><p><strong>Importance: </strong>With emerging new variants of concern (VOC), SARS-CoV-2 continues to be a major threat to human health. Approved COVID-19 vaccines have been less effective against these emerging VOCs. This work demonstrates the protective efficacy and strong boosting effect of an intranasal viral-vectored vaccine against SARS-CoV-2 variants in hamsters. Our intranasal vaccine can act as an effective booster for individuals already 58 vaccinated against SARS-CoV-2.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0198924"},"PeriodicalIF":4.0,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674033","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":"Development of ferret immune repertoire reference resources and single-cell-based high-throughput profiling assays.","authors":"Evan S Walsh, Kui Yang, Tammy S Tollison, Sujatha Seenu, Nicole Adams, Guilhem Zeitoun, Ifigeneia Sideri, Geraldine Folch, Hayden N Brochu, Hsuan Chou, Sofia Kossida, Ian A York, Xinxia Peng","doi":"10.1128/jvi.00181-25","DOIUrl":"https://doi.org/10.1128/jvi.00181-25","url":null,"abstract":"<p><p>Domestic ferrets (<i>Mustela putorius furo</i>) are important for modeling human respiratory diseases. However, ferret B and T cell receptors have not been completely identified or annotated, limiting immune repertoire studies. Here, we performed long-read transcriptome sequencing of ferret splenocyte and lymph node samples to obtain over 120,000 high-quality full-length immunoglobin (Ig) and T cell receptor (TCR) transcripts. We constructed a complete reference set of the constant regions of ferret Ig and TCR isotypes and chain types. We also systematically annotated germline Ig and TCR variable (V), diversity (D), joining (J), and constant (C) genes on a recent ferret reference genome assembly. We designed new ferret-specific immune repertoire profiling assays by targeting positions in constant regions without allelic diversity across 11 ferret genome assemblies and experimentally validated them using a commercially compatible single-cell-based platform. These improved resources and assays will enable future studies to fully capture ferret immune repertoire diversity.IMPORTANCEDomestic ferrets (<i>Mustela putorius furo</i>) are an increasingly common model organism to study human respiratory diseases such as influenza infections. However, researchers lack ferret-specific reagents and resources to study the immune system and immune response in ferrets. In this study, we developed comprehensive ferret immune repertoire reference resources and assays, which will enable more accurate analyses of the ferret immune system in the future.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0018125"},"PeriodicalIF":4.0,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674017","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}