Journal of Virology最新文献

{"title":"Comparison of Ebola virus infection routes and resulting disease in animal models.","authors":"B Ryder Gathright, Andrea Marzi","doi":"10.1128/jvi.00081-26","DOIUrl":"https://doi.org/10.1128/jvi.00081-26","url":null,"abstract":"<p><p>Ebola virus disease (EVD) is a highly pathogenic and lethal disease caused by Ebola virus (EBOV). Endemic to Sub-Saharan Africa, EBOV has been causing global health concerns during infrequent EVD outbreaks since 1976, particularly during the 2013 -2016 epidemic in West Africa. Spread by contact of contaminated bodily fluids with mucous membranes or breaks in the skin, EBOV yields an incredibly high mortality rate and, as a result, has been designated a priority pathogen and a select agent to be studied exclusively in maximum containment laboratories. EBOV has historically been studied in animal models that accurately recapitulate disease progression, symptoms, and outcomes as seen in humans via more artificial infection routes such as intramuscular (IM) and intraperitoneal (IP) inoculation. There has recently been a concerted effort to characterize disease in animal models with mucosal inoculation routes with the goal to more accurately replicate human infection and development of EVD. This review aims to summarize and characterize the different inoculation routes used in the various animal models applied in EBOV research. We also outline the differences in disease progression between \"artificial\" and mucosal infection routes, comparing them to the course of EVD as seen in humans to highlight similarities and differences.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0008126"},"PeriodicalIF":3.8,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816341","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":"Tylvalosin tartrate inhibits PRRSV replication by suppressing cellular pyroptosis through the TLR4/NF-κB signaling pathway.","authors":"Shi-Qin Zhang, Xin-Lei Li, Cheng Yang, Dao-Wen Li, Xiao-Hong Deng, Wei Hu, Xing-Yao Pei, Wen-Juan Zhang, Xiao-Xue Yu, Ying-Feng Sun","doi":"10.1128/jvi.00202-26","DOIUrl":"https://doi.org/10.1128/jvi.00202-26","url":null,"abstract":"<p><p>Tylvalosin tartrate, a potent antimicrobial agent, is clinically observed to mitigate porcine reproductive and respiratory syndrome virus (PRRSV) infection, yet its mechanism remains unclear. Here, we demonstrate that tylvalosin tartrate treatment significantly reduces serum viremia and inflammatory cytokine production, correlating with symptom alleviation in piglets infected with lineage 1 (L1) PRRSV. <i>In vitro</i>, it effectively inhibits the replication of not only L1 PRRSV but also other major lineage strains (L8.1/CH-1a-like, L5/VR2332-like, and L8.3/JXA1-like) in porcine alveolar macrophages (PAMs). Transcriptomic analysis suggested that tylvalosin tartrate suppresses PRRSV replication by inhibiting cellular pyroptosis. We confirmed that L1 PRRSV infection induces pyroptosis in PAMs, and viral replication was hindered upon inhibition of caspase-1 (CASP1) or gasdermin D (GSDMD). Tylvalosin tartrate inhibited GSDMD-mediated pyroptosis induced by either L1 PRRSV or lipopolysaccharide (LPS)/nigericin. Further investigation revealed that tylvalosin tartrate acts upstream by suppressing the activation of the TLR4/NF-κB signaling pathway, a key driver of inflammatory gene expression and pyroptosis. Pharmacological inhibition of TLR4 using resatorvid and genetic knockdown through siRNA replicated the antiviral and anti-pyroptotic effects of tylvalosin tartrate. Our findings elucidate a host-directed mechanism by which tylvalosin tartrate restricts PRRSV replication across diverse lineages, highlighting its potential as a multifaceted therapeutic agent against PRRSV infection.IMPORTANCEPorcine reproductive and respiratory syndrome (PRRS) causes enormous economic losses worldwide. Controlling PRRSV is challenging due to viral genetic diversity, limited vaccine efficacy, and the lack of specific antiviral drugs. Tylvalosin tartrate, a widely used veterinary antibiotic for respiratory and enteric diseases, has been empirically observed to improve outcomes in PRRSV-affected herds. This study provides novel mechanistic evidence that tylvalosin tartrate possesses direct, broad-spectrum antiviral activity against PRRSV by targeting a host pathway. We show that it inhibits viral replication across major epidemic lineages by dampening the TLR4/NF-κB signaling axis and the subsequent gasdermin D (GSDMD)-dependent pyroptosis. This \"old drug, new use\" strategy repurposes an approved, safe compound to counteract both viral replication and excessive inflammation-a hallmark of severe PRRS. Our work not only clarifies the molecular basis for its clinical utility but also positions tylvalosin tartrate as a promising host-targeted antiviral and immunomodulatory agent for PRRS management, offering a practical and immediate intervention strategy for the swine industry.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0020226"},"PeriodicalIF":3.8,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775290","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":"Protective human antibodies against Powassan virus.","authors":"Georgia Fallon, Stefanie P Muraro, Samuel Ailsworth, Sean Hui, Ryan J Malonis, Alexandra L Tse, Emily Happy Miller, Kartik Chandran, Daved H Fremont, Michael S Diamond, Jonathan R Lai","doi":"10.1128/jvi.02105-25","DOIUrl":"https://doi.org/10.1128/jvi.02105-25","url":null,"abstract":"<p><p>Powassan virus (POWV) is a tick-borne orthoflavivirus that can cause severe neuroinvasive disease. There are no approved vaccines or therapeutics, and the incidence of POWV infection in humans is rising. Here, we isolated and characterized a panel of human monoclonal antibodies (mAbs) from a convalescent donor using single B-cell sorting with POWV EDIII and full-length E ectodomain as antigen bait. Binding and neutralization assays with both POWV reporter virus particles and an authentic strain identified multiple neutralizing mAbs that target distinct epitopes across the E glycoprotein, including EDIII lateral ridge/C-C' loop and non-EDIII regions. Four neutralizing mAbs were evaluated in a lethal mouse challenge, two of which conferred substantial protection. These findings define key targets of the human antibody response to POWV and highlight candidates for the development of human monoclonal antibody therapy for this emerging virus.</p><p><strong>Importance: </strong>Powassan virus is an emerging tick-borne orthoflavivirus with steadily increasing case numbers. With an approximately 10% case-fatality rate and no approved therapeutics or vaccines available, POWV represents a potential public health threat. Our results showing that human monoclonal antibodies can protect mice against POWV in a lethal challenge model provide a foundation for developing future effective immunotherapies against this virus.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0210525"},"PeriodicalIF":3.8,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775086","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":"Evolution-guided prioritization identifies a tissue-specific phosphorylation switch on herpes simplex virus 1 UL7 regulating viral replication and pathogenicity.","authors":"Akihisa Kato, Takanori Tannaka, Ryoji Iwasaki, Saori Shio, Shaocong Liu, Kousuke Takeshima, Yuhei Maruzuru, Yasushi Kawaguchi","doi":"10.1128/jvi.00200-26","DOIUrl":"https://doi.org/10.1128/jvi.00200-26","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Although numerous phosphorylation sites on herpes simplex virus 1 (HSV-1) proteins have been identified through phosphoproteomic analyses, their virological significance remains largely unclear. Here, we developed an evolution-guided prioritization strategy that integrates phosphoproteomic data with residue-level conservation across the genus &lt;i&gt;Simplexvirus&lt;/i&gt; to identify phosphorylation sites as candidates for functional relevance. Applying this strategy to a previously reported phosphoproteomic data set, we identified 46 phosphorylation sites with a conservation level of 88% or higher. Among them, we focused on two phosphorylation sites, UL6 Tyr-234 and UL7 Tyr-89, which are conserved in 100% and 88% of &lt;i&gt;Simplexvirus&lt;/i&gt; species, respectively. Phosphomimetic mutations at either site significantly reduced progeny virus yields in cultured cells, suggesting that phosphorylation at these sites can function as an inhibitory switch regulating HSV-1 replication. In agreement with this, in-depth analyses of phosphorylation at UL7 Tyr-89 during HSV-1 infection revealed that the phosphomimetic mutation led to phenotypes similar to those of the UL7 null mutation in virion morphogenesis, HSV-1 replication in the central nervous system (CNS) and eyes of mice, as well as CNS pathogenicity and ocular pathogenic manifestations. Notably, the non-phosphorylatable mutation at this site had little effect on HSV-1 infection in cultured cells, whereas it significantly reduced HSV-1 replication and pathogenicity in the CNS, but not in the eyes of mice. These results suggest that our strategy effectively prioritizes phosphorylation sites for functional investigation and that phosphorylation at UL7 Tyr-89 serves as a context-dependent inhibitory switch, fine-tuning UL7 activity in a tissue-specific manner, particularly in the CNS.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;Intricate phosphorylation-dependent regulatory mechanisms enable viruses to diversify the functions of their proteins, profoundly shaping viral replication and pathogenicity. Although phosphoproteomic analyses have produced an expanding catalog of phosphorylation sites on viral proteins, a considerable proportion of these modifications are likely non-functional. This creates a pressing need for a prioritization strategy to predict functionally relevant phosphorylation sites. To address this, we developed an evolution-guided prioritization strategy that integrates phosphoproteomic data with genus-level conservation. Using this strategy, we prioritized two tyrosine phosphorylation sites for functional analysis. Notably, phosphorylation at one of these sites, UL7 Tyr-89, functions as a tissue-specific regulatory mechanism that fine-tunes UL7 activity and modulates herpes simplex virus 1 replication and pathogenicity in the central nervous system. This strategy provides a practical framework for prioritizing candidate regulatory sites for functional investigation in viral replication and pathogenicity.","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0020026"},"PeriodicalIF":3.8,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147774576","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":"Is the molecular microenvironment of the latent HIV reservoir predictable using deep learning approaches?","authors":"Heng-Chang Chen","doi":"10.1128/jvi.00175-26","DOIUrl":"https://doi.org/10.1128/jvi.00175-26","url":null,"abstract":"<p><p>Although current antiretroviral therapy effectively suppresses viral replication in infected individuals, infections remain incurable. One of the main reasons for this is the uncertainty of the molecular microenvironment of the latent HIV reservoir. If this microenvironment can be precisely targeted, the effectiveness of current antiretroviral therapy can be leveraged. To better depict the potent microenvironments of the latent HIV reservoir, it is crucial to first understand the mechanisms that make some viruses transcriptionally active and others silent in the first place. It is currently feasible to predict gene activity from DNA sequence, coupled with epigenetics, using deep learning approaches. Substantial progress has been made in creating multidimensional data sets related to the HIV latent reservoir. The implementation of deep learning to mine potent attributes, enabling the characterization and prediction of the microenvironment of the latent HIV reservoir, is thus imperative. This minireview discusses potent features that can be integrated into deep learning methodologies to predict the likelihood of the potential microenvironment from different tiered levels of the latent HIV reservoir organization, and proposes the principal workflow to tackle this question using deep learning approaches.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0017526"},"PeriodicalIF":3.8,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147774867","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":"RANBP3 and RAN orchestrate CRM1-mediated nuclear export of hepatitis B virus RNAs.","authors":"Mengfei Wang, Quan Chen, Yingcheng Zheng, Jiatong Yin, Guoguo Zhu, Kaitao Zhao, Zaichao Xu, Rong Hua, Meng Zhou, Lu Zhang, Gaihong Zhao, Shipeng Yang, Zulihuma Amat, Yuchen Xia, Xiaoming Cheng","doi":"10.1128/jvi.00267-26","DOIUrl":"https://doi.org/10.1128/jvi.00267-26","url":null,"abstract":"<p><p>Nuclear export of viral RNAs is essential for the replication of hepatitis B virus (HBV). Our previous study demonstrated that ELAVL1 (embryonic lethal, abnormal vision, Drosophila-like 1) mediates the nuclear export of HBV RNAs via the chromosome region maintenance 1 (CRM1) pathway by recognizing and binding to the AUUUA motifs within these transcripts. Here, we identify Ras-related nuclear protein (RAN) and RAN-binding protein 3 (RANBP3) as critical downstream regulators of this CRM1-mediated RNA export pathway. We show that RANBP3 recruits RAN-GTP to assemble an export-competent quaternary complex (CRM1-HBV RNAs-RANBP3-RAN-GTP). The functional significance of this complex is underscored by the findings that its disruption, through knockdown of RANBP3/RAN, or by introducing CRM1 mutations that prevent cofactor binding, severely impairs HBV RNA export and viral replication. Together, our study thus elucidates a precise regulatory mechanism governing HBV RNA trafficking and highlights RANBP3 and RAN as potential antiviral targets.IMPORTANCEEfficient nuclear export of hepatitis B virus (HBV) RNAs is essential for viral replication, yet the regulatory mechanisms controlling this process remain poorly defined. This study identifies Ras-related nuclear protein (RAN) and RAN-binding protein 3 (RANBP3) as key host cofactors that drive chromosome region maintenance 1 (CRM1)-mediated export of HBV transcripts by assembling an export-competent complex with viral RNAs. Disrupting this pathway profoundly impairs RNA export and downstream steps of the viral life cycle. By defining how HBV harnesses the RANBP3-RAN-CRM1 axis for RNA trafficking, our work reveals a previously unrecognized layer of host dependency and highlights RANBP3 and RAN as promising targets for antiviral intervention.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0026726"},"PeriodicalIF":3.8,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775103","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":"Mapping hemagglutinin residues driving antigenic diversity in H5Nx avian influenza viruses.","authors":"Rebecca Daines, Jean-Remy Sadeyen, Pengxiang Chang, Munir Iqbal","doi":"10.1128/jvi.00095-26","DOIUrl":"https://doi.org/10.1128/jvi.00095-26","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Since its emergence in 1996, the H5 avian influenza virus (AIV) A/Goose/Guangdong/1/1996 (Gs/GD) hemagglutinin (HA) has evolved into over 30 genetically and antigenically distinct clades, including the widespread clade 2.3.4.4b. Vaccination is widely used in endemic regions to reduce poultry losses and zoonotic risk. However, the evolving antigenic diversity and global co-circulation of multiple clades challenge the protective efficacy of poultry vaccines with poor antigenic matching to field strains, resulting in immune escape and vaccine failure. This study aimed to improve vaccine seed selection by identifying HA epitopes contributing to inter-clade antigenic differences. Recombinant clade-representative viruses were generated using HA genes from circulating H5 AIVs via reverse genetics with A/Puerto Rico/8/1934 (PR8) internal and neuraminidase genes. Antigenic relationships were assessed using hemagglutination inhibition (HI) assays with homologous and heterologous chicken antisera. Antigenic cartography revealed a clear distinction of clade 2.3.4.4 from others and notable intra-clade diversity. Pairwise antigenic and genetic comparisons identified 48 putative antigenic residues. These were individually introduced into a candidate HA by site-directed mutagenesis, and antigenic influence was assessed by HI using sera raised against the non-mutated HA. Four residues R82K, A83T, T204I, and F229Y had significant antigenic effects, with three (R82K, T204I, and F229Y [H5 numbering]) being novel. These findings demonstrate that combining serology and &lt;i&gt;in silico&lt;/i&gt; residue analysis can identify key antigenic determinants. This work highlights the need for precise antigenic matching in vaccine design and highlights the value of combining molecular and immunological tools to optimize vaccine seed selection against diverse and evolving H5 strains.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;The continued evolution of H5 avian influenza viruses (AIVs), particularly the Gs/GD lineage, poses major challenges for poultry disease control and zoonotic risk mitigation. Vaccine effectiveness is undermined by antigenic drift and the co-circulation of diverse clades, often leading to mismatches between vaccine and field strains. This study addresses the critical need to improve vaccine strain selection by identifying hemagglutinin (HA) residues driving antigenic variation across H5 clades. Using recombinant viruses, antigenic cartography, hemagglutination inhibition assays, and mutagenesis, we pinpointed 48 key residues, with four R82K, A83T, T204I, and F229Y having major antigenic effects, including three novel markers. These findings advance our understanding of H5 antigenic evolution and provide a framework for predicting vaccine performance. By integrating molecular and serological data, our work informs rational vaccine seed strain selection, contributing to more broadly protective vaccines and improved control of H5 AIV in poultry, while reducing the risk o","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0009526"},"PeriodicalIF":3.8,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816461","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":"JMJD6-mediated epigenetic silencing of innate immunity promotes pseudorabies virus replication.","authors":"Sheng-Li Ming, Ya-Jing Chai, Jia-Ming Yang, Jia-You Xing, Shi-Jun Zhang, Sai-Nan He, Qing-Xia Lu, Jiang Wang, Jia-Jia Pan, Wei-Fei Lu, Lei Zeng, Bei-Bei Chu","doi":"10.1128/jvi.00028-26","DOIUrl":"https://doi.org/10.1128/jvi.00028-26","url":null,"abstract":"<p><p>Jumonji domain-containing protein 6 (JMJD6) has been implicated in epigenetic regulation. Here, we demonstrated that JMJD6 was upregulated during pseudorabies virus (PRV) infection and critically enhanced viral replication by promoting virion release. Mechanistically, JMJD6 suppressed PRV-induced histone H4K16 acetylation, a modification associated with chromatin relaxation and DNA damage response activation. This epigenetic modulation attenuated the cGAS-STING-mediated innate immune signaling pathway, leading to reduced interferon production and enhanced viral propagation. Furthermore, we identified METTL23 as a nuclear interactor of JMJD6 upon viral infection, revealing a cooperative role between these proteins in facilitating immune evasion. Importantly, administration of the JMJD6-specific inhibitor JMJD6-IN-1 potently activated innate immunity and restricted PRV replication in mice. Our findings unveil a novel epigenetic strategy employed by PRV to evade host antiviral responses and highlight JMJD6 as a potential therapeutic target for combating herpesvirus infections.IMPORTANCEThe ongoing conflict between viruses and host antiviral defenses is central to viral pathogenesis. Pseudorabies virus (PRV), a highly contagious alphaherpesvirus, causes severe economic losses in the global swine industry and poses an emerging zoonotic threat to humans. This study identifies the epigenetic modulator, the JMJD6, as a critical host factor exploited by PRV to evade antiviral immunity. Our work uncovers a previously unrecognized epigenetic strategy employed by herpesviruses and establishes JMJD6 as a promising target for developing broad-spectrum antivirals against PRV and related pathogenic herpesviruses.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0002826"},"PeriodicalIF":3.8,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147774893","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":"Pseudovirus-mediated proximity labeling identifies candidate host cell membrane proteins involved in viral attachment.","authors":"Norihiro Kotani, Kensuke Iwasa, Tomoko Amimoto, Chikara Yamashita, Kumiko Komatsu, Yutaka Narimichi, Yoshiki Wakabayashi, Yuuki Kurebayashi, Yutaka Horiuchi, Leona Kashimata, Ryoko Sasaki, Megumi Kumagai, Nan Yagishita-Kyo, Takeo Awaji, Takashi Murakami, Yosuke Mizuno, Miyako Nakano, Tadanobu Takahashi, Hideyuki Takeuchi, Koichi Honke","doi":"10.1128/jvi.00507-26","DOIUrl":"https://doi.org/10.1128/jvi.00507-26","url":null,"abstract":"<p><p>Viral infections pose a significant threat to humanity, as exemplified by the COVID-19 pandemic. To mitigate the associated damage, understanding the biological characteristics of causative viruses is essential. In this study, we report a novel method for identifying host cell molecules (including virus receptors) required for viral attachment, referred to as host cell attachment factors (HCAFs). Our approach utilizes proximity labeling (PL) technology; pseudoviruses engineered to express a PL enzyme are applied to host cells, where they bind and initiate PL. Because HCAFs are expected to localize near viral attachment sites, candidate HCAFs were specifically tagged using the PL process. The analysis of influenza HCAFs enabled the identification of multiple candidate molecules. Subsequent viral attachment experiments using Chinese hamster ovary cells suggested that neuropilin-1 may serve as an HCAF for influenza viruses. Given its simplicity and rapid turnaround, this method is adaptable to a wide range of enveloped viruses, including pandemic viruses that require emergency analyses.IMPORTANCEIdentifying cellular receptors for viruses is not only crucial in conventional virology research but also plays a key role in addressing pandemic viruses. The significance of our work lies in establishing a standardized method for viral receptor identification, an area in which no widely accepted protocol has previously existed, by utilizing pseudovirus-mediated proximity labeling technology. Moreover, this approach provides a highly versatile platform that enables rapid and low-cost identification of viral receptors.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0050726"},"PeriodicalIF":3.8,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775074","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":"Nairobi sheep disease virus: an emerging threat with unresolved pathogenesis and zoonotic potential.","authors":"Xue-Lian Zhang, Meng-Hang Wang, Jia-Hao Hu, De-Xin Liang, Xin Yin, Jian-Wei Shao","doi":"10.1128/jvi.00330-26","DOIUrl":"https://doi.org/10.1128/jvi.00330-26","url":null,"abstract":"<p><p>Nairobi sheep disease virus (NSDV), a tick-borne orthonairovirus, causes severe hemorrhagic disease in small ruminants with mortality rates reaching 90% in naïve populations. Its recent emergence in China, the world's largest small ruminant producer, marks a significant eastward expansion and poses immediate threats to global food security and animal health. This escalating crisis, however, stands in stark contrast to critical gaps in understanding the virus's molecular pathogenesis. The mechanisms governing cellular entry, innate immune evasion, and induction of lethal vascular pathology remain poorly characterized, severely hampering countermeasure development. This review synthesizes the current epidemiological landscape of NSDV and delineates key knowledge gaps in its molecular biology. We place particular emphasis on the unexplored viral life cycle and the host response and conclude by proposing a prioritized research agenda aimed at bridging these mechanistic gaps. Within a One Health framework, such efforts are essential to mitigate the veterinary, economic, and potential zoonotic impacts of this emerging arthropod-borne threat.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0033026"},"PeriodicalIF":3.8,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147774896","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}