Journal of Virology最新文献

{"title":"Limited adaptive mutations but deterministic genome formula variation in bluetongue virus.","authors":"Yannis Moreau, Patricia Gil, Antoni Exbrayat, Ignace Rakotoarivony, Emmanuel Bréard, Corinne Sailleau, Cyril Viarouge, Stephan Zientara, Giovanni Savini, Maria Goffredo, Giuseppe Mancini, Etienne Loire, Serafin Gutierrez","doi":"10.1128/jvi.00983-26","DOIUrl":"https://doi.org/10.1128/jvi.00983-26","url":null,"abstract":"<p><p>Arthropod-borne viruses or arboviruses alternate between vertebrates and arthropods, facing distinct selection pressures in each host. Surprisingly, mechanisms facilitating host alternation remain unstudied. Here, we investigate two phenomena potentially facilitating host alternation in bluetongue virus (BTV): adaptive mutations and genome formula variation (GFV; i.e., differences in segment copy numbers). First, we searched for mutations indicative of host adaptation in cattle, sheep, and midges infected during an epizootic. No mutation was fixed in all samples of a given host. Thus, adaptive mutations may not be a major mechanism facilitating host alternation in the studied epizootic. Second, we investigated the relationship between GFV and a proxy of viral fitness, namely, head infection in midges. We analyzed the genome formula (GF) in <i>Culicoides imicola</i> midges, either with or without head infection 10 days after oral inoculation. GFs differed between dissemination groups, suggesting a correlation between GF and head infection. Finally, we investigated the mechanisms underlying GF generation. Currently, two scenarios have been proposed: random generation followed by selection or directed generation through molecular mechanisms. To limit the influence of selection, we analyzed the GF after a single replication cycle in cell culture. GFs converged toward specific values across replicates. Moreover, GFs differed between arthropod and vertebrate cells. Thus, GF generation does not seem purely stochastic and is probably influenced by host-specific mechanisms. Overall, our findings highlight GFV as a mechanism potentially facilitating host alternation of BTV, and they do not strongly support an involvement of mutations in the same phenomenon.IMPORTANCEArthropod-borne viruses are major public health concerns worldwide. These viruses follow a complex cycle involving an alternation between arthropods and vertebrates. Surprisingly, little is known about the mechanisms that could facilitate this alternation. Understanding such mechanisms could aid the development of antiviral strategies. Here, using bluetongue virus as a model, we investigated two potential mechanisms facilitating alternation. These mechanisms are adaptive mutations and genome formula variation (GFV). We found limited evidence for host-specific parallel mutations in natural populations from a single epizootic. In contrast, we observed a potential link between GFV and viral fitness. Moreover, our results suggest that molecular mechanisms generate host-specific genome formulas from the first round of cell infection.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0098326"},"PeriodicalIF":4.1,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182779","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":"mRNA-LNP delivery of a homo-tandem nanobody protects goslings from novel goose astrovirus infection.","authors":"Dan Wang, Xianyu Shao, Yi Ai, Lebin Han, Huarui Liu, Xinlong Zhang, Ang Lin, Qiyun Zhu","doi":"10.1128/jvi.01127-26","DOIUrl":"https://doi.org/10.1128/jvi.01127-26","url":null,"abstract":"<p><p>Novel goose astrovirus (nGAstV) infection causes visceral gout and high mortality in goslings, but at present, there are no effective vaccines or antiviral agents. Here, we identified a neutralizing nanobody (Nb60) targeting the spike (P2) protein of nGAstV capable of inhibiting viral replication by blocking both viral attachment and entry. For effective <i>in vivo</i> delivery, we designed an mRNA-encoded homo-tandem nanobody (3×Nb60) flanked by an Anser interleukin-2 (IL-2) signal peptide and Anser untranslated regions that exhibited an approximately twofold improvement in neutralization potency compared to the mRNA-encoded Nb60 monomer. The mRNA encoding nanobody was encapsulated with lipid nanoparticles (LNPs) to prolong its half-life in serum by approximately 48 h. In a gosling infection model, the 3×Nb60 mRNA-LNP (2 mg/kg) produced 100% survival for both prophylaxis and therapy, significantly reduced viral shedding and viral loads in tissues, attenuated hepatic and renal pathology, and restored serum uric acid, alanine aminotransferase, and aspartate aminotransferase levels to close to the baseline values. Epitope mapping revealed that Nb60 recognizes a critical conformational epitope on the P2 protein, with residues 529R and 553G being essential for binding. The findings establish an mRNA-encoded nanobody platform as a promising strategy for prophylaxis and therapy in the early stages of nGAstV infection.IMPORTANCENovel goose astrovirus (nGAstV) has caused widespread outbreaks of visceral gout in goslings across China since 2017, leading to substantial economic losses in the poultry industry. The disease predominantly affects goslings under 3 weeks of age, and the short disease course limits the utility of conventional vaccines. This study establishes an mRNA-encoded nanobody (Nb) platform in which avian-specific regulatory elements, including an Anser IL-2 signal peptide and an Anser globin untranslated region, enable efficient expression of a neutralizing Nb60 in avian cells. A homo-tandem design (3×Nb60) further prolongs the <i>in vivo</i> half-life, improves antiviral potency, and provides complete protection in goslings. By offering a species-matched delivery framework, this platform provides a rapid-response strategy for emerging avian viral diseases and may also shed light on the development of mRNA-encoded antibody therapeutics against human enteric viruses.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0112726"},"PeriodicalIF":4.1,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181805","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":"Primer: Human T-cell leukemia virus type 1 (HTLV-1).","authors":"Charles R M Bangham, Masao Matsuoka","doi":"10.1128/jvi.01183-26","DOIUrl":"https://doi.org/10.1128/jvi.01183-26","url":null,"abstract":"<p><p>The human T-cell leukemia virus HTLV-1-also known as human T-lymphotropic virus type 1-was the first human retrovirus discovered. Unlike HIV-1, it has been present in humans for tens of thousands of years, and in consequence HTLV-1 is exquisitely adapted to persist in the individual host. Its life history therefore differs fundamentally from that of HIV-1 in key respects. HTLV-1 causes an aggressive hematological malignancy known as adult T-cell leukemia-lymphoma (ATL) and a progressive inflammatory disease of the central nervous system, HTLV-1-associated myelopathy (HAM), in a proportion of infected people. These conditions impose a significant health burden in countries where the virus is endemic.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0118326"},"PeriodicalIF":4.1,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182082","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":"Variant escape site mapping and characterization of SARS-CoV-2 nucleocapsid rapid antigen test antibodies.","authors":"Alasdair D Keith, Meredith M Keen, Filipp Frank, Wilbur A Lam, Morgan Greenleaf, Eric A Ortlund","doi":"10.1128/jvi.01001-26","DOIUrl":"https://doi.org/10.1128/jvi.01001-26","url":null,"abstract":"<p><p>Rapid antigen tests (RATs) were a critical tool for diagnosing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the height of the pandemic, but their performance depends on antibodies that remain robust to viral evolution. Since most commercial RATs target the viral nucleocapsid protein, mutations in this domain can compromise binding and test performance. To systematically define this risk, we used deep mutational scanning (DMS) to map escape mutations for 82 antibodies across 43 commercially available tests, generating the most comprehensive escape database of SARS-CoV-2 viral mutations to date. Most antibodies target conformational epitopes, with 47 (57%) mapping to the RNA-binding domain and 23 (28%) to the dimerization domain. Principal component analysis and clustering revealed escape phenotypes, including shared features outside of predicted epitopes. As the pandemic proceeded, we noted a change in industry preference from IgG to IgM-type antibodies, which was associated with changes to epitope sub-class prevalence. Analysis of paired capture-detection antibodies revealed a preference for targeting the same structural domain (20/33 or 61%), indicating a slight preference for test antibodies to hit orthogonal yet proximal sites. Together, the results establish a comprehensive resource for understanding how SARS-CoV-2 nucleocapsid protein mutations affect antibody binding and the phenotypes that underlie RAT antibody selection. This resource and approach can help prioritize antibodies for follow-up performance testing and support the design of more mutation-resilient diagnostics.IMPORTANCEIt is critical during a pandemic for diagnostic tests to be accurate and for the false negative rate to be kept low. The rapidly changing nature of SARS-CoV-2 exposed a weakness with using rapid antigen tests to diagnose infection, as mutations to the viral nucleocapsid protein can cause the virus to evade detection. In this work, we systematically tested the robustness of 82 antibodies from 43 separate commercially available tests by deliberately mutating the nucleocapsid protein and investigating which changes caused weakened binding to the test antibodies. In addition to determining which specific tests were at risk from certain mutations, we collated our datasets into a meta-analysis, allowing us to identify some best practices for designing robust tests. We, therefore, expect that this resource will support the design of more mutation-resilient diagnostics, whether for future variants of SARS-CoV-2 or in applying these principles to other respiratory viruses, such as influenza virus.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0100126"},"PeriodicalIF":4.1,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182474","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":"Primer: Functions and evolution of viral proteins.","authors":"Eugene V Koonin, Mart Krupovic","doi":"10.1128/jvi.01202-26","DOIUrl":"https://doi.org/10.1128/jvi.01202-26","url":null,"abstract":"<p><p>Viruses encode an enormous variety of proteins that jointly comprise the largest pool of protein diversity on Earth. At coarse grain, the viral pan-proteome can be partitioned into four classes of proteins that differ in their evolutionary conservation, spread across the virosphere, and broadly defined functionality: (i) viral hallmark proteins (VHPs) that are broadly conserved across different realms of viruses, (ii) proteins responsible for core viral functions, such as replication, expression, and virion structure, but are more narrowly represented within a single virus realm, kingdom, or phylum, (iii) fast-evolving proteins involved in virus-host interactions, particularly counter-defense, that are typically conserved only in narrow groups of viruses, (iv) \"dark matter,\" that is, proteins without detectable homologs or known functions, typically shared only by closely related viruses. Apart from the few VHPs that might descend from the primordial protein pool, most of the viral proteins are derived from cellular ancestors, via recruitment of proteins with activities relevant for virus replication, and extensive exaptation. The recruitment of cellular proteins for roles in viral reproduction follows a logic dictated by the functionalities that are relevant for viruses. Thus, different groups of viruses often convergently capture distinct, sometimes unrelated proteins, providing similar activities, for example, polymerases, helicases, and proteases of different families. Recent advances in protein structure prediction and analysis provide unprecedented insights into the organization and evolution of the viral pan-proteome.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0120226"},"PeriodicalIF":4.1,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181813","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":"Primer: Giant viruses of protists.","authors":"Jonatas Santos Abrahao","doi":"10.1128/jvi.01257-26","DOIUrl":"https://doi.org/10.1128/jvi.01257-26","url":null,"abstract":"<p><p>Giant viruses infecting protists have expanded our understanding of viral diversity. These members of the phylum <i>Nucleocytoviricota</i> possess genomes that can exceed 2.5 Mb and encode hundreds to thousands of proteins, including functions once thought unique to cellular organisms. They infect amoebae, algae, and other unicellular eukaryotes, forming large factories and interacting with virophages and mobile genetic elements. Their virions display diverse architectures, from icosahedral particles to amphora-shaped pandoraviruses and tail-bearing tupanviruses. Comparative genomics highlights evolutionary processes such as horizontal gene transfer, gene duplication, <i>de novo</i> gene birth, and genome rearrangements, which contribute to their genomic diversity. Despite their widespread presence in aquatic and terrestrial ecosystems, many aspects of their biology remain unknown, including the roles of lineage-specific ORFan genes (open reading frames with no detectable homologs in current databases) and the molecular strategies used to manipulate hosts. This minireview provides an accessible overview of protist-infecting giant viruses, summarizing their classification, virion architecture, replication strategies, and evolutionary scenarios, and points to key questions that remain open.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0125726"},"PeriodicalIF":4.1,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181907","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":"Beyond independent roles: spatiotemporal coupling between viral fusion proteins and viroporins in viral replication and host inflammation.","authors":"Jiaqi Li, Yuan Sun, Hua-Ji Qiu, Su Li","doi":"10.1128/jvi.01013-26","DOIUrl":"https://doi.org/10.1128/jvi.01013-26","url":null,"abstract":"<p><p>Membrane fusion and permeabilization are key membrane remodeling processes hijacked by viruses. Although fusion proteins and viroporins have long been characterized as discrete functional modules, emerging evidence supports the spatiotemporal coordination through shared regulation of ion flux, pH homeostasis, membrane tension, organelle stress, and vesicular trafficking during viral infections. These synchronized membrane events synergistically shape viral replication and host immune responses. This review establishes a fusion-ion-inflammation axis to guide mechanistic exploration and antiviral drug development.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0101326"},"PeriodicalIF":4.1,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182732","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":"Revisiting mRNA capping in <i>Mononegavirales</i>: a promising, yet underexplored antiviral target.","authors":"Khadijah Khan, Mohammad Ejaz Adil, Monika Antil, Dilip Kumar","doi":"10.1128/jvi.01025-26","DOIUrl":"https://doi.org/10.1128/jvi.01025-26","url":null,"abstract":"<p><p>mRNA capping is a co-transcriptional, nuclear process in eukaryotes that adds a cap onto the 5' end of RNA to confer stability, efficient translation, and nuclear export. Viruses have evolved diverse strategies by mimicking or subverting host pathways to install an mRNA cap for efficient gene expression and evasion of the host innate immune response. The conventional mRNA capping pathway, employed by many RNA and DNA viruses, is mediated by dedicated RNA 5'-triphosphatase, guanylyltransferase, and methyltransferase enzymes. In contrast, many RNA viruses utilize unconventional capping mechanisms that diverge from the canonical pathway, offering unique opportunities to develop virus family-specific antiviral therapeutics. Among negative-sense RNA viruses, members of the order <i>Mononegavirales</i> harbor a unique capping domain, polyribonucleotidyltransferase (PRNTase), embedded within the viral RdRp large (L) protein. Unlike the conventional guanylyltransferase-mediated mechanism, PRNTase catalyzes mRNA capping through the formation of a covalent L-pRNA intermediate rather than the canonical GMP-enzyme intermediate. The HR motif in PRNTase, involved in covalent linking to mRNA, is highly conserved in non-segmented negative-strand RNA viruses. This review focuses on structural and functional insights into <i>Mononegavirales</i> capping, highlighting the conserved motifs and domain architecture that make it a promising therapeutic target.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0102526"},"PeriodicalIF":4.1,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182385","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":"Avian influenza A virus polymerase gene leads to temperature-resistant genome replication.","authors":"Stephanie L Williams, Sebastian M Gygli, Jacob C Bjorgen, Haitian Fan, Munashe Mudiwa, Lex Matthews, Yongli Xiao, Ashley Freeman, Sharon F Legaspi, Li Qi, Jeffery K Taubenberger, Ervin Fodor","doi":"10.1128/jvi.00978-26","DOIUrl":"https://doi.org/10.1128/jvi.00978-26","url":null,"abstract":"<p><p>Influenza A viruses (IAV) pose a persistent pandemic threat. Successful cross-species transmission from waterfowl to mammals requires host adaptation for efficient replication and spread. Avian IAVs are adapted to the temperature of the avian gut, approximately 41°C, while human IAVs replicate at 33°C in the upper respiratory tract. PB1, the catalytic core of the viral heterotrimeric RNA-dependent RNA polymerase (RdRp), is essential for viral RNA synthesis. Three pandemic IAV strains (1918, 1957, and 1968) carried an avian-origin PB1 gene, suggesting a selective advantage. Fever, a critical antiviral response, elevates body temperature to 38°C or higher and can restrict viral replication. We hypothesized that avian PB1 may allow IAV replication at febrile temperatures. Using a mini-replicon system, we demonstrate that a polymerase of a seasonal human H1N1 IAV fails to replicate viral RNA efficiently at 40°C, whereas substitution of the PB1 with that from the 1918, 1957, and 1968 pandemic viruses, or a low-pathogenic avian H2N1 virus, restores RNA synthesis. Chimeric seasonal human H1N1 viruses expressing avian or 1918 PB1 replicate at 40°C in MDCK cells, unlike wild-type H1N1. Activity assays with purified chimeric IAV polymerases further suggest that avian-origin PB1 may intrinsically enhance polymerase activity at elevated temperatures. Together, these data show that avian-origin PB1 enables IAV replication at febrile temperatures, highlighting its role in zoonotic emergence and host adaptation. Surveillance of avian-origin PB1 genes in IAVs circulating in mammals may help identify strains with pandemic potential and inform the development of countermeasures.IMPORTANCEInfluenza A viruses of avian origin remain a persistent threat to human health. The 1918, 1957, and 1968 pandemic influenza viruses each acquired an avian-origin PB1 gene, but the adaptive advantage conferred by these genes remains incompletely understood. Here, we show that avian-origin PB1 genes enhance viral RNA replication by a seasonal human influenza virus polymerase at elevated temperature and enable replication of a human influenza virus at 40°C, a temperature relevant to both avian hosts and human febrile illness. PB1-dependent effects were observed in cell-based polymerase assays, with purified polymerase, and during authentic virus infection. These findings identify temperature-resistant genome replication as a potential adaptive property of avian-origin PB1 and suggest that acquisition of an avian PB1 may help influenza viruses overcome temperature barriers encountered during adaptation to mammalian hosts.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0097826"},"PeriodicalIF":4.1,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182721","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":"Superinfection exclusion strategy of siphophage T5: analysis of the FhuA:Llp complex.","authors":"Séraphine Degroux, Corinne Vivès, Emeline Mestdach, Claudine Darnault, Aline le Roy, Caroline Mas, Loïc Salmon, Torsten Herrmann, Cécile Breyton","doi":"10.1128/jvi.00909-26","DOIUrl":"https://doi.org/10.1128/jvi.00909-26","url":null,"abstract":"<p><p>Superinfection exclusion is a widespread viral mechanism that protects the infected cell from overinfection by other identical or closely related viruses. Shortly after infection by bacteriophage T5, the bacterium <i>Escherichia coli</i> produces Llp, encoded by the newly injected viral genome. Llp is a small lipoprotein targeted to the inner leaflet of the host outer membrane. It binds to FhuA, an outer-membrane iron-ferrichrome transporter, which is the T5 receptor at the <i>E. coli</i> cell surface. The interaction between Llp and FhuA prevents any further bacteriophage binding and infection. Here, we determined the NMR structure of Llp and analyzed the formation of the FhuA:Llp complex using a wide range of techniques and mutants, both <i>in vivo</i> and <i>in vitro</i>. Interaction of Llp with FhuA is governed by a two-step equilibrium with a strong contribution of induced fit: Llp binding requires remodeling of FhuA periplasmic plug surface, enabling the subsequent large conformational reorganization of the extracellular loops. Analysis of FhuA mutants shows the importance of the intertwined interactions between the extracellular loops and the plug in the communication between the periplasmic and the extracellular faces of FhuA.IMPORTANCEBacteriophages (phages) are viruses that infect bacteria. As their enemies, phages play an important role in the dynamics, diversity, evolution, and pathogenicity of bacterial populations, but also represent an alternative to antibiotics in our fight against the rise of multi-resistant pathogenic bacterial strains. Infection is triggered by phage recognition of a receptor at the host surface, inducing phage DNA injection into the bacterial cytoplasm. The host cell is then transformed into a viral factory. To secure this viral factory, the infecting phage develops superinfection exclusion strategies, preventing other phages from interfering. Understanding how phages achieve the \"locking\" of the host will allow us to optimize phage use in phage therapy. Here, we analyze the structure of the receptor-exclusion protein complex using integrated <i>in vivo</i>, biochemical, and biophysical approaches. Our analysis reveals an unusually slow association process, consistent with an induced-fit mechanism, ultimately transmitting information from the bacterial periplasm to its surface.</p>","PeriodicalId":17583,"journal":{"name":"Journal of Virology","volume":" ","pages":"e0090926"},"PeriodicalIF":4.1,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167220","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}