Journal of Virology最新文献

{"title":"Retraction for Saeed et al., \"Parvulin 14 and Parvulin 17 Bind to HBx and cccDNA and Upregulate Hepatitis B Virus Replication from cccDNA to Virion in an HBx-Dependent Manner\".","authors":"Umar Saeed, Jumi Kim, Zahra Zahid Piracha, Hyeonjoong Kwon, Jaesung Jung, Yong-Joon Chwae, Sun Park, Ho-Joon Shin, Kyongmin Kim","doi":"10.1128/jvi.01187-25","DOIUrl":"https://doi.org/10.1128/jvi.01187-25","url":null,"abstract":"","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0118725"},"PeriodicalIF":3.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040543","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":"Broad-spectrum vaccines against various and evolving viruses: from antigen design to nanoparticle delivery.","authors":"Mengxiang Cao, Yongfeng Li, Xin Song, Zhanhao Lu, Huanjie Zhai, Hua-Ji Qiu, Yuan Sun","doi":"10.1128/jvi.00997-25","DOIUrl":"https://doi.org/10.1128/jvi.00997-25","url":null,"abstract":"<p><p>Pathogen evolution and narrow vaccine coverage urgently demand broad-spectrum vaccines. This review explores two pivotal technological fronts: structural biology- and immunoinformatics-guided antigen design, and utilizing nanoparticle-based delivery systems to induce broad immune responses. We critically analyze four antigen optimization strategies: (i) structure-based antigen design, (ii) conserved epitope targeting, (iii) consensus sequence-based antigen engineering, and (iv) chimeric immunogen design. Additionally, the common types and characteristics of nanoparticles are described briefly. Subsequently, we delve into cutting-edge applications of nanoparticles to enhance immune protection, including mosaic and cocktail nanoparticle vaccines, surface-modified targeting strategies, and the integration of mRNA technology with virus-like particles (VLPs). In conclusion, this review synthesizes risk-benefit analyses of existing strategies, current challenges, and emerging opportunities, offering practical frameworks to facilitate broad-spectrum vaccine innovation and enhance pandemic preparedness.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0099725"},"PeriodicalIF":3.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040545","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":"Retraction for Piracha et al., \"Sirtuin 2 Isoform 1 Enhances Hepatitis B Virus RNA Transcription and DNA Synthesis through the AKT/GSK-3β/β-Catenin Signaling Pathway\".","authors":"Zahra Zahid Piracha, Hyeonjoong Kwon, Umar Saeed, Jumi Kim, Jaesung Jung, Yong-Joon Chwae, Sun Park, Ho-Joon Shin, Kyongmin Kim","doi":"10.1128/jvi.01186-25","DOIUrl":"https://doi.org/10.1128/jvi.01186-25","url":null,"abstract":"","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0118625"},"PeriodicalIF":3.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040576","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":"Ebola virus' hidden target: virus transmission to and infection of skin.","authors":"Paige T Richards, Anthony M Fleck, Radhika Patel, Maryam Fakhimi, Dana Bohan, Kathleen Geoghegan-Barek, Anna N Honko, Allison E Stolte, Caroline B Plescia, Caitlin O Messingham, Samuel J Connell, Tyler P Crowe, Francoise A Gourronc, Ricardo Carrion, Anthony Griffiths, David K Meyerholz, Aloysius J Klingelhutz, Robert A Davey, Kelly N Messingham, Wendy Maury","doi":"10.1128/jvi.01300-25","DOIUrl":"https://doi.org/10.1128/jvi.01300-25","url":null,"abstract":"<p><p>Ebola virus (EBOV), the causative agent of Ebola virus disease, remains one of the World Health Organization's top 10 threats to global health. Infectious EBOV virions can be found on the surface of skin late in infection and may be transmitted to others through skin-to-skin contact. We investigate <i>in vivo</i> EBOV tropism and the kinetics of virus movement to and from the skin. Increasing viral loads were detected over time in the skin of EBOV-infected non-human primates and mice, with antigen detected in dermal stromal and immune cells. Epidermal cells within and surrounding hair follicles also harbored viral antigen, suggesting a novel mechanism of virus egress to the epidermal surface. During late infection, proinflammatory responses were elevated in infected visceral organs but minimal in the skin despite significant viral loads. We observed similar viral trafficking and cell tropism in the skin of mice intraperitoneally infected with a low containment EBOV model virus, rVSV/EBOV GP, allowing more detailed mechanistic studies. Sites of virus infection in the skin were patchy, with intense focal areas of infection surrounded by uninfected areas. To investigate virus entry into the body through skin, rVSV/EBOV GP was applied to the surface of gently abraded skin to remove the stratum corneum; epidermal keratinocytes were robustly infected with subsequent systemic viral dissemination observed in some mice. Optimal levels of infection within the skin required expression of the phosphatidylserine receptor, AXL. Collectively, our data demonstrate that skin serves as an important organ targeted by EBOV, facilitating virus entry into and egress from the body.IMPORTANCEEbola virus (EBOV) remains one of the World Health Organization's top 10 threats to global health, despite the availability of a U.S. Food and Drug Administration-approved vaccine. EBOV spreads through human-to-human contact, yet the role of skin in viral transmission remains unclear. Here, we identify skin as a site of EBOV infection, serving as a potential portal for entry into and egress from the body. <i>In vivo</i>, infectious virions and viral RNA increased in the skin over time, localizing to dermal myeloid and stromal cells and to cells within and surrounding hair follicles, suggesting a novel mechanism for viral shedding. Skin infection was patchy and associated with minimal inflammation, despite significant viral loads. Using a surrogate EBOV model, we demonstrate that systemic infection can occur following topical administration through abraded skin and requires phosphatidylserine receptor, AXL, for optimal infection of skin. These findings redefine the role of skin in EBOV pathogenesis, with implications for barrier-targeted interventions.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0130025"},"PeriodicalIF":3.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040606","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":"From phenotype to receptor: validating physiological clustering of <i>Escherichia coli</i> phages through comprehensive receptor analysis.","authors":"Tomoyoshi Kaneko, Toshifumi Osaka, Minoru Inagaki, Kento Habe, Takuma Okabe, Satoshi Tsuneda","doi":"10.1128/jvi.01061-25","DOIUrl":"https://doi.org/10.1128/jvi.01061-25","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Understanding the relationship between bacteriophage (phage) classification and target receptors is crucial for phage ecology and applied research. In this study, we compared 13 previously isolated &lt;i&gt;Escherichia coli&lt;/i&gt; phages based on physiological characteristics, whole-genome sequences, and tail fiber protein phylogenetics. We improved our previously proposed physiological clustering method by optimizing the bacterial panel for host range assessment, implementing appropriate distance metrics for mixed data types, and applying silhouette coefficient analysis for objective determination of optimal cluster numbers. We combined genomic analysis and lipopolysaccharide (LPS) structural analysis of phage-resistant &lt;i&gt;E. coli&lt;/i&gt; strains to identify target receptors of the phages. Complementation experiments further confirmed the direct involvement of identified genes in phage reception. The results revealed that phylogenetically distinct &lt;i&gt;E. coli&lt;/i&gt; phages target different sites in the LPS R-core region (modified by WaaV, WaaW, WaaT, and WaaY), membrane proteins (NfrB, TolA, YhaH), or flagella. Our analysis revealed that subtle chemical modifications of LPS (such as heptose phosphorylation) were shown to be important for &lt;i&gt;E. coli&lt;/i&gt; phage recognition. Furthermore, physiological characteristics, tail fiber phylogenetics, and whole genome analysis independently classified the phages with high correlation to target receptor specificity. The addition of three phages with known receptors further validated our approach. Our results suggest that grouping based on physiological characteristics (such as lysis dynamics and host range) and genotypes (tail fiber phylogenetics or whole genome analysis) independently classified phages with high correlation to target receptor specificity. Here, we elucidated the diversity and specificity of &lt;i&gt;E. coli&lt;/i&gt; phage target receptors, providing new insights into the classification of &lt;i&gt;E. coli&lt;/i&gt; phages and phage-host interactions.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;Phage therapy is gaining attention as an alternative treatment for antibiotic-resistant bacteria. Developing effective phage cocktails requires combining phages with different target receptors, but traditional methods for identifying target receptors are labor-intensive. This study demonstrates that E. coli phages targeting the TK001 strain with different target receptors can be grouped based on their physiological characteristics, tail fiber sequences, or whole genomes. Our approach was enhanced through systematic bacterial panel selection for host range assessment, optimized distance metrics for physiological characteristics, and objective cluster determination using silhouette coefficient analysis for all three classifications. This insight can be used to more efficiently create diverse phage cocktails. Additionally, we identified phages targeting diverse sites, including different regions of LPS, membrane proteins, and flagella. These find","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0106125"},"PeriodicalIF":3.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033635","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":"Solution structure of the C-terminal domain of the measles virus V protein in its free form and mechanistic analysis of STAT2 targeting.","authors":"Kaho Morita, Nanaka Goda, Madoka Kimoto, Satomi Inaba-Inoue, Nana Yabuno, Aoi Sugiyama, Hiroyuki Kumeta, Toyoyuki Ose","doi":"10.1128/jvi.00739-25","DOIUrl":"https://doi.org/10.1128/jvi.00739-25","url":null,"abstract":"<p><p>Viruses commonly evade the host antiviral interferon (IFN) response by targeting key components of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway, typically STAT1 and STAT2. Among the well-characterized viral IFN antagonists, measles virus (MeV), a member of the <i>Morbillivirus</i> genus, encodes a multifunctional V protein (MeV-V) that directly interacts with STAT proteins. The C-terminal domain (CTD) of MeV-V selectively binds to STAT2, disrupting the formation of the IFN-stimulated gene factor 3 (ISGF3) complex by inhibiting the STAT2-interferon regulatory factor 9 (IRF9) association. Here, we report a solution structure covering the MeV-V_CTD in its unbound form, as determined by nuclear magnetic resonance spectroscopy. While the overall architecture, including a distinctive zinc-finger motif, conforms to previously predicted features, our analysis reveals unexpected features, including distinct proline <i>cis</i> conformers that may have functional relevance. Molecular mapping analysis, combined with relaxation measurements, identified key residues implicated in STAT2 recognition and revealed substantial conformational flexibility within the domain. These findings suggest that MeV-V_CTD employs a shared binding surface for STAT2 binding as for melanoma differentiation-associated protein 5 (MDA5) interaction, underscoring its structural adaptability. As V proteins across <i>Morbillivirus</i> species engage diverse host pathways, including immune signaling, cell cycle regulation, and apoptosis, by targeting multiple proteins, we propose that the dynamic yet folded nature of the V_CTD underlies its ability to serve as a versatile interaction module in host-pathogen interplay.IMPORTANCEThe measles virus V protein, encoded by the P gene, orchestrates the broad modulation of host responses, including immune evasion, by interacting with multiple host factors. With regard to structural studies of V_CTD, to date, only one protein from parainfluenza virus 5 has been crystallographically analyzed in complex with host targets. Despite the conserved nature of the V_CTD among paramyxoviruses, structural information on the unbound state of this domain is lacking, and current insights largely rely on computational predictions based on the structure of the bound form. Our nuclear magnetic resonance work provides the first structure of the V_CTD from paramyxoviruses in its free form. In accordance with our previously presented data, we further confirmed that the MeV-V binding site of STAT2 overlaps that of IRF9. The conformational flexibility observed within the folded CTD provides the structural basis for its ability to engage with multiple host targets with high specificity.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0073925"},"PeriodicalIF":3.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033670","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":"A recombinant Marek's disease vaccine candidate provides complete protection against infectious bursal disease virus and H9 subtype avian influenza virus in chickens.","authors":"Wenrui Fan, Xianying Zeng, Yuntong Chen, Qingqing Yu, Zibo Zhang, Guobin Tian, Changjun Liu, Hongmei Bao, Xiaole Qi, Longbo Wu, Yanping Zhang, Yongzhen Liu, Suyan Wang, Hongyu Cui, Yulu Duan, Hualan Chen, Yulong Gao","doi":"10.1128/jvi.01149-25","DOIUrl":"https://doi.org/10.1128/jvi.01149-25","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Vaccination is the most effective preventative measure against economically devastating poultry diseases, such as infectious bursal disease (IBD), H9 subtype avian influenza (AI), and Marek's disease. In recent decades, various vaccination strategies have been investigated and developed. Among these, multivalent and combination vaccines, which confer protection against multiple diseases in a single dose, have emerged as a significant advancement in veterinary medicine. This study demonstrates that the attenuated Marek's disease virus serotype 1 (MDV-1) vaccine strain, rMSΔMeq, known for its safety and robust carrier immunogenicity, can serve as a vector for the heterologous expression of multiple antigenic proteins. We constructed the recombinant virus rMDV-VP2-HA by inserting the H9 subtype avian influenza virus (AIV) hemagglutinin (HA) expression cassette into the UL41 region and the infectious bursal disease virus (IBDV) VP2 expression cassette into the US2 region. The growth characteristics of this recombinant virus were consistent with those of the parental virus, and it stably expressed the HA and VP2 genes. Vaccination with rMDV-VP2-HA induces high titers of IBDV-neutralizing antibodies and hemagglutinin inhibition (HI) antibodies and elicits strong cellular immune responses. Specifically, vaccination with rMDV-VP2-HA enhances interferon-gamma (IFN-γ) expression in response to stimulation with HA and VP2 proteins. Meanwhile, cytokines associated with both Th1 and Th2 responses were also upregulated. Remarkably, chickens vaccinated with rMDV-VP2-HA achieved complete protection against very virulent IBDV, H9 subtype AIV, and very virulent MDV. These findings underscore the exceptional practical potential of rMDV-VP2-HA as the first MDV-1 vector-based multivalent vaccine candidate for combating these poultry diseases.IMPORTANCECommercial vaccines for infectious bursal disease (IBD) and H9 subtype avian influenza (AI) require multiple doses, increasing costs and causing stress in chicken flocks. Additionally, their efficacy is frequently compromised by maternal antibody interference. This underscores the urgent need for a multivalent, multi-component, and single-dose vaccines capable of streamlining immunization protocols, overcoming maternal antibody interference, and providing lifelong immunity. Our research demonstrates, for the first time, serotype 1 Marek's disease virus (MDV-1) can stably express multiple exogenous genes. More significantly, the rMDV-VP2-HA elicits robust humoral and cellular immune responses, achieving complete protection against H9 subtype AIV, very virulent IBDV, and very virulent MDV with a single immunization. These findings contribute to enhancing the efficiency of disease prevention and confirm that the MDV-1 is an ideal vector for developing multivalent vaccines, achieving the goal of \"multiple protections with a single shot.\" This advancement represents a significant progression in the prevention and contr","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0114925"},"PeriodicalIF":3.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033690","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":"The mammalian SKI complex is a broad-spectrum antiviral drug target that upregulates cellular cholesterol to inhibit viral replication.","authors":"Stuart Weston, Lauren Baracco, Louis Taylor, Alison J Scott, Gaurav Kumar, Paul Shapiro, Alexander D MacKerell, Matthew B Frieman","doi":"10.1128/jvi.01323-25","DOIUrl":"https://doi.org/10.1128/jvi.01323-25","url":null,"abstract":"<p><p>There is a need for the development of broad-spectrum antiviral compounds that can act as first-line therapeutic countermeasures to emerging viral infections. Host-directed approaches present a promising avenue of development and carry the benefit of mitigating risks of viral escape mutants. We have previously found the SKI (super killer) complex to be a broad-spectrum, host-target with our lead compound (\"UMB18\") showing activity against influenza A virus, coronaviruses, and filoviruses. The SKI complex is a cytosolic RNA helicase, and we previously found that UMB18 inhibited viral RNA production but did not further define the mechanism. Here, we demonstrate that UMB18 directly binds to SKIC8 of the SKI complex, and transcriptomic analysis of UMB18-treated A549 cells revealed an upregulation of genes in the mevalonate pathway, which drives cholesterol synthesis. Further investigation validated the genetic upregulation and confirmed an increase in total cellular cholesterol. This upregulation was dependent on the sterol regulatory element-binding proteins (SREBPs) and their regulator SCAP, the major regulators for cholesterol and fatty acid synthesis. Depletion of the SREBPs or SCAP with siRNA, or extraction of cholesterol with methyl β-cyclodextrin, attenuated UMB18 antiviral activity, emphasizing the role of increased cholesterol synthesis in this mechanism of action. Our findings further define the antiviral mechanism of a developmental host-directed therapeutic approach with broad applicability against emerging viral pathogens.</p><p><strong>Importance: </strong>The COVID-19 pandemic has underscored the need for effective countermeasures to emerging pathogens. Our research builds upon our published data on a novel antiviral compound termed UMB18. We have found UMB18 capable of inhibiting replication of influenza A virus, coronaviruses, and the filoviruses Marburg and Ebola virus, but did not fully define a mechanism of action. Here, we demonstrate that UMB18 exerts antiviral activity by modulating cellular cholesterol levels. By targeting the SKI complex, UMB18 triggers an increase in endogenous cellular cholesterol, which disrupts the fine balance that viruses rely on for efficient infection. We demonstrate that this mechanism inhibits replication of SARS-CoV-2, revealing a previously undescribed host-directed strategy for antiviral intervention. These findings highlight UMB18's potential as a broad-spectrum antiviral agent and pave the way for further research into its mechanism and therapeutic applications, offering a promising avenue for development of antiviral countermeasures to current, novel, and emerging pathogens.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0132325"},"PeriodicalIF":3.8,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030116","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":"Oropouche virus NSs protein suppresses host transcription by targeting the RNA polymerase II RPB1 protein.","authors":"Eduardo Jurado-Cobena, Cigdem Alkan, Tetsuro Ikegami","doi":"10.1128/jvi.01176-25","DOIUrl":"https://doi.org/10.1128/jvi.01176-25","url":null,"abstract":"<p><p>Oropouche fever is a debilitating disease caused by Oropouche virus (OROV), an arthropod-borne member of the Peribunyaviridae family. Despite its public health significance, the molecular mechanisms driving OROV pathogenesis remain poorly understood. In other bunyaviruses, the nonstructural NSs protein encoded by the small (S) genome segment acts as a major virulence factor. In this study, infection with the OROV MD023 strain led to nuclear accumulation of NSs and redistribution of nucleophosmin 1 (NPM1) from the nucleolus. OROV infection suppressed nascent RNA synthesis and resulted in decreased levels of the RNA polymerase II (RNAP II) subunit RPB1, along with reduced phosphorylation of its C-terminal domain (CTD) at serine 2 and serine 5 residues. When expressed from a recombinant Rift Valley fever virus MP-12 strain, OROV NSs colocalized with NPM1 and contributed to its nucleolar redistribution. Furthermore, expression of OROV NSs induced a marked reduction in the hyperphosphorylated RNAP IIo form, which was largely restored upon treatment with the proteasome inhibitor MG132. These findings suggest that OROV NSs promote RNAP II degradation and suppress host transcription, underscoring its potential role in modulating host responses during infection.</p><p><strong>Importance: </strong>Oropouche fever is a viral disease characterized by fever, headaches, and body aches, affecting thousands of people in tropical regions. The Oropouche virus (OROV) has caused and continues to cause medium to large-scale outbreaks, highlighting the urgent need to better understand its basic biology. This study focused on the viral NSs protein, which modulates host antiviral responses. Our findings demonstrate that NSs disrupt RNA polymerase II, a key enzyme in host gene expression, by reducing its activity and stability. Additionally, OROV infection alters the nucleolus, a critical center for cellular stress responses and ribosome biogenesis. These disruptions suggest that OROV suppresses host transcription and nucleolar function, thereby impairing the cellular antiviral response. Understanding these mechanisms provides new insights into host-virus interactions and viral strategies for modulating host cell responses.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0117625"},"PeriodicalIF":3.8,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030064","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":"Replication-competent adenovirus reporters utilizing endogenous viral expression architecture.","authors":"Claire M O'Brien, Lorenzo Serra, Molly R Patterson, Reyes W Acosta, Alison Yu, Daniel T Claiborne, Alexander M Price","doi":"10.1128/jvi.01146-25","DOIUrl":"https://doi.org/10.1128/jvi.01146-25","url":null,"abstract":"<p><p>Adenoviruses are double-stranded DNA viruses widely used as platforms for vaccines, oncolytics, and gene delivery. However, tools for studying adenoviral gene expression in real time during infection remain limited. Here, we describe a set of fluorescent and bioluminescent reporter viruses built using the modular AdenoBuilder reverse genetics system and informed by high-resolution maps of Ad5 transcription. These reporters utilize endogenous early and late transcriptional units, enabling visualization of viral gene expression without exogenous promoters or splicing elements. These model viruses replicate with kinetics nearly indistinguishable from wild-type virus and have enabled real-time fluorescent imaging as well as longitudinal bioluminescent sampling from the same infected samples. Together, this next generation of adenovirus reporters provides a modular and tractable platform for studying viral gene regulation and replication dynamics in real time, with broad applications for basic research and high-throughput screening.</p><p><strong>Importance: </strong>This research provides powerful new tools to rapidly study adenovirus gene expression and replication. By integrating fluorescent and secreted luciferase reporters into native viral regulatory elements, we enable real-time, non-destructive tracking of early and late stage infection in living cells. These modular reporters are compatible with a wide range of genetic and chemical perturbations, allowing researchers to investigate the function of specific viral genes, host interactions, and the impact of host genes and antiviral compounds. Importantly, the high-throughput nature of these systems overcomes limitations of traditional plaque assays to quantify viral replication dynamics. Our work will allow for the rapid creation of both novel infectious and replication-incompetent viral vectors.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0114625"},"PeriodicalIF":3.8,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030086","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}