Journal of General Virology最新文献

{"title":"Longitudinal detection and genetic characterization of feline coronavirus in a captive cheetah population.","authors":"Tomoyoshi Doki, Yusaku Shimomura, Kanna Kitakami, Tomohiro Tateishi, Miki Ozaki, Sae Omori, Kenta Tsukui, Tomomi Takano","doi":"10.1099/jgv.0.002317","DOIUrl":"10.1099/jgv.0.002317","url":null,"abstract":"<p><p>Feline coronavirus (FCoV) infections, including fatal feline infectious peritonitis (FIP), have been documented in captive cheetahs (<i>Acinonyx jubatus</i>), but longitudinal data on viral circulation and genetic diversity in this species remain limited. In this study, we performed a 3.5-year molecular epidemiological investigation of a closed captive cheetah cohort at a single zoological facility in Japan. Non-invasive monitoring of 17 individually identified cheetahs by reverse-transcription quantitative PCR of faecal samples revealed long-term maintenance of FCoV in the population, with highly variable individual-specific viral RNA detection patterns over time. Phylogenetic analysis of near-complete genomes recovered from an asymptomatic shedder and an FIP-affected individual placed the cheetah-derived viruses within the type I FCoV clade. Targeted sequencing of the partial nucleocapsid gene identified 17 nt haplotypes and revealed viral sequence diversity and temporal changes in the dominant consensus haplotypes detected within individual cheetahs. These temporal changes could not distinguish reinfection from within-host evolution or undetected within-sample viral diversity. Analysis of the spike (S) gene showed marked regional differences in sequence diversity: the S1/S2 cleavage site region contained 16 nt haplotypes, whereas the S2 1058/1060 region contained only 4 nt haplotypes and showed lower diversity. Tissue-derived sequences from the FIP-affected cheetah were assigned to defined haplotypes within the population-level haplotype framework. Together, these data show that FCoV was maintained for multiple years in this closed cheetah cohort and that faecal surveillance combined with targeted sequencing can track temporal changes in the dominant FCoV sequences detected in captive non-domestic felids.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 8","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13466200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148727748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T-cell immunoglobulin and mucin domain 1 and transmembrane serine protease 2 synergistically enhance entry of a bat-derived merbecovirus.","authors":"Misa Katayama, Kaikin Li, Ayano Ichikawa, Yuta Wakabayashi, Wataru Sekine, Akiko Takenaka-Uema, Taisuke Horimoto, Shin Murakami","doi":"10.1099/jgv.0.002299","DOIUrl":"10.1099/jgv.0.002299","url":null,"abstract":"<p><p>Phosphatidylserine (PS) receptors facilitate entry of diverse enveloped viruses and have been implicated in enhancing coronavirus attachment, including for SARS-CoV-2, yet their precise contribution remains unclear. We examined this pathway using EjCoV-3, a recently identified bat merbecovirus. Exogenous PS, but not phosphatidylcholine, reduced viral infectivity in a concentration-dependent manner, suggesting competitive inhibition of receptor binding by virion-associated PS. T-cell immunoglobulin and mucin domain 1 (TIM-1) knockout (KO) in Vero/TMPRSS2 (transmembrane protease, serine 2) cells markedly reduced early viral infection. TIM-1 KO cells also showed markedly reduced virion attachment, indicating that TIM-1 acts as a PS-dependent attachment factor. Growth kinetics further revealed that TIM-1 contributes to efficient EjCoV-3 replication under conditions without exogenous protease and accelerates early viral growth in the presence of exogenous protease. A549 cells and A549/hACE2 cells are not susceptible to EjCoV-3 infection in the absence of exogenous proteases, and sustained viral replication was observed only when TIM-1 and TMPRSS2 were co-expressed, indicating that the two proteins synergistically promote infection. However, the expression of either factor alone was insufficient to sustain sustained viral replication. In contrast, in A549/EnACE2 cells, an EjCoV-3-susceptible cell line expressing a more compatible bat angiotensin-converting enzyme 2 (ACE2) orthologue, even in the absence of exogenous proteases, the expression of TMPRSS2 enhanced infection, whereas the expression of TIM-1 had no effect. These findings indicate that in environments where only low-affinity receptors are present, TIM-1 promotes EjCoV-3 infection primarily through PS-mediated attachment and functions in concert with TMPRSS2-dependent spike activation. This cooperative mechanism may reduce receptor barriers and enhance the potential for cross-species transmission of bat-derived coronaviruses, thereby contributing to their emergence as zoonotic pathogens.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 8","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13451038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148689234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of bovine-derived H5N1 viruses expressing fluorescent and luminescent reporter proteins.","authors":"Mohammed Nooruzzaman, Pablo Sebastian Britto de Oliveira, Chen Feng, Diego G Diel","doi":"10.1099/jgv.0.002298","DOIUrl":"10.1099/jgv.0.002298","url":null,"abstract":"<p><p>Highly pathogenic avian influenza H5N1 clade 2.3.4.4b viruses present a broad host range, with recent spillover and sustained transmission in dairy cattle reported in the USA. Replication-competent reporter viruses are critical tools that enable real-time monitoring of virus replication, facilitating high-throughput screens. In this study, we engineered three recombinant H5N1 clade 2.3.4.4b reporter viruses expressing nanoluciferase (NLuc) and two fluorescent reporter proteins, miniGFP2 and UnaG within the open reading frame of the nonstructural gene of the bovine A/Cattle/Texas/063224-24-1/2024 (TX2/24) virus. All reporter viruses replicated efficiently <i>in vitro</i>, presenting replication kinetics comparable to the parental rTX2/24 virus, but exhibited smaller plaque sizes, suggesting reduced cell-to-cell spread. <i>In vivo</i> infection studies in mice showed comparable pathogenicity among all four viruses, although rTX2/24-miniGFP2 and rTX2/24-UnaG exhibited decreased virus shedding relative to rTX2/24 and rTX2/24-NLuc. Virus titrations and <i>in situ</i> localization of virus replication sites demonstrated robust replication in respiratory tissues, with slightly attenuated systemic dissemination of all three reporter viruses. Fluorescent virus neutralization assays using miniGFP2 and UnaG reporter viruses accurately quantified neutralizing antibody titres in sera from naturally infected dairy cattle, consistent with wild-type virus assays. Additionally, the utility of the NLuc reporter virus for antiviral screening was validated against oseltamivir <i>in vitro</i>. Collectively, these results establish the H5N1 TX2/24-based reporter viruses as versatile and biologically relevant tools for investigating H5N1 pathogenesis and for use in serological and antiviral drug screens.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 7","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13379244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Variability and population structure of watermelon mosaic virus in zucchini crops in Poland.","authors":"Daria Budzyńska, Julia Minicka, Aleksandra Zarzyńska-Nowak, Martyna Szkatulska, Agnieszka Taberska, Beata Hasiów-Jaroszewska","doi":"10.1099/jgv.0.002273","DOIUrl":"10.1099/jgv.0.002273","url":null,"abstract":"<p><p>Watermelon mosaic virus (species <i>Potyvirus citrulli</i>, WMV) poses a significant threat to various cucurbit species worldwide. In Poland, the virus has been consistently recorded in <i>Cucurbita pepo</i> var. <i>giromontiina</i> crops since 2008. To analyse the genetic diversity and population structure of WMV in Poland, comprehensive surveys were conducted in two major agricultural regions, Greater Poland and Kuyavian-Pomeranian Voivodeships (west-central and mid-northern regions of Poland, respectively). To better understand the WMV occurrence, over 1,800 leaf samples were randomly collected from symptomatic and asymptomatic zucchini and weed plants. Moreover, aphids were also analysed for the presence of the virus. In this study, 154 complete coat protein gene sequences of WMV isolates collected between 2013 and 2024 were obtained using Sanger or high-throughput sequencing. The sequence identity of the Polish WMV isolates ranged from 92.8 to 100% and 95.4 to 100% for nucleotide and amino acid sequences, respectively. Unique mutations were identified in the isolates originating from the Kuyavian-Pomeranian region. Moreover, a novel KEET motif was identified in nine isolates, which has not been reported in previous studies. Most CP codons undergo negative selection; however, eight positively selected sites were detected. Phylogenetic analysis revealed that the Polish isolates were grouped in both classical and emergent main phylogenetic clades. The population analyses indicated limited or no gene flow between WMV subpopulations, suggesting that genetic drift may be considered an important evolutionary force shaping the viral diversity.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 7","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13378793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148375910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ICTV Virus Taxonomy Profile: <i>Konkoviridae</i> 2026.","authors":"Yutaro Neriya, Laura Miozzi, Anna Maria Vaira, Yasuhiro Tomitaka, Takahide Sasaya","doi":"10.1099/jgv.0.002290","DOIUrl":"10.1099/jgv.0.002290","url":null,"abstract":"<p><p><i>Konkoviridae</i> is a family of negative-sense RNA viruses with genomes of 8.7-10.6 kb that have been associated with plants. Virions are filamentous in the shape of kinked circles. The konkovirus genome consists of three or four segments with three to six ORFs that encode a large protein (L) containing an RNA-directed RNA polymerase domain, a nucleoprotein, a putative cell-to-cell movement protein and additional one to three non-structural proteins of unknown function. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family <i>Konkoviridae</i>, which is available at ictv.global/report/konkoviridae.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 7","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13343855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Data mining reveals the diversity of prophage endolysins targeting pathogenic enterococci.","authors":"Finn O'Dea, Andrew Kinsella, Brooks J Rady, Andrew D Millard, Joseph Brown, Graham P Stafford, Stéphane Mesnage","doi":"10.1099/jgv.0.002292","DOIUrl":"10.1099/jgv.0.002292","url":null,"abstract":"<p><p>Antimicrobial resistance poses a critical global health threat, with enterococci among the leading contributors due to their intrinsic and acquired resistance to antibiotics. Clinically relevant species, including <i>Enterococcus faecalis</i> and <i>Enterococcus faecium</i> as well as the emerging poultry pathogen <i>Enterococcus cecorum</i>, highlight the need for alternative therapeutics across human and agricultural settings. Bacteriophages and their derived enzymes, particularly endolysins, offer promising antibacterial strategies but challenges such as phage resistance and limited lysin diversity hinder their application. In this study, we performed a large-scale analysis of prophage-encoded endolysins across these three enterococcal opportunistic pathogens, characterizing over 48,000 sequences. We identified 33 distinct domain architectures combining diverse catalytic and cell wall-binding domains (CBDs) including novel putative CBDs. These findings expand the known diversity of enterococcal lysins and provide a comprehensive resource for the rational design of stable, recombinant 'enzybiotics' to combat multidrug-resistant enterococcal infections.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 7","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13379245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bovine α-herpesvirus 1 replication and immediate early transcription unit 1 promoter are jointly stimulated by glucocorticoid receptor and DNA-dependent ATPases.","authors":"Fouad S El-Mayet, Mike St Clair, Brooke Costello, Jeffery B Ostler, Clinton Jones","doi":"10.1099/jgv.0.002301","DOIUrl":"10.1099/jgv.0.002301","url":null,"abstract":"<p><p>Bovine α-herpesvirus 1 (BoHV-1) is a significant viral pathogen in cattle and cofactor of bovine respiratory disease (BRD), a polymicrobial disease. Annually, BRD directly costs the U.S. cattle industry ~$1 billion. Following acute infection, BoHV-1 establishes latency in sensory neurons in trigeminal ganglia, non-neuronal cells in pharyngeal tonsil and certain neurons in the brain. The synthetic corticosteroid dexamethasone (DEX) consistently induces reactivation from latency. The immediate early transcription unit 1 (IEtu1) promoter drives expression of two important viral transcriptional regulatory proteins, infected cell protein 0 (bICP0) and bICP4. An early promoter also drives bICP0 expression. The IEtu1 promoter is activated by the glucocorticoid receptor (GR) and other stress-induced cellular transcription factors because it contains two functional glucocorticoid response elements (GREs). Brahma (BRM) and Brahma-related gene 1 (BRG1) are associated with the SWItch/Sucrose-NonFermentable chromatin remodelling complex. Since BRM and BRG1 interact with GR, we hypothesized that BRG1 and/or BRM stimulate viral gene expression and replication. GR and BRG1 or BRM, cooperatively transactivated an IEtu1 <i>cis</i>-regulatory module that contains both GREs. BoHV-1 replication was also significantly reduced by a BRG1 and/or BRM siRNA or a specific BRG1 and BRM inhibitor (BRM014). Chromatin immunoprecipitation studies revealed that BRG1 occupies IEtu1 promoter sequences only when cells express GR and are treated with DEX. In summary, these studies revealed that GR and the BRG1/BRM chromatin-remodelling proteins cooperatively transactivated the IEtu1 promoter and stimulated BoHV-1 productive infection.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 7","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13372059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148447370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human pegivirus, Toscana virus and herpesviruses identified in cerebrospinal fluid from adults with unexplained neurologic disease, Spain, 2022-2023.","authors":"Ana Donoso, Ana Belén Pérez, Marcos Lopez-Dosil, Ana Vázquez, Fabiana Gámbaro, María Paz Sánchez-Seco, Luis Martinez-Martinez, Maria Cabrerizo, David Tarragó, Maria Dolores Fernandez-Garcia","doi":"10.1099/jgv.0.002302","DOIUrl":"10.1099/jgv.0.002302","url":null,"abstract":"<p><p>Viral central nervous system (CNS) infections in adults frequently remain unresolved after routine diagnostic testing. We applied probe-based viral metagenomic next-generation sequencing (vmNGS) to cerebrospinal fluid samples from adults with suspected CNS infection and negative conventional diagnostics in a retrospective multicentre study conducted in Spain between 2022 and 2023. Among 40 idiopathic cases, vmNGS detected viral sequences in 6 patients without evidence of coinfection: human pegivirus (HPgV, <i>n</i>=3), Toscana virus (TOSV, <i>n</i>=1), herpes simplex virus type 1 (HSV-1, <i>n</i>=1) and varicella-zoster virus (VZV, <i>n</i>=1). Two HPgV-positive patients were transplant recipients, with neurological disease occurring more than 2 years after transplantation, compatible with possible long-term viral persistence in immunocompromised hosts. TOSV genotype B was identified in a patient residing in central Spain, supporting consideration of TOSV in selected cases of unexplained aseptic meningitis during the vector season, including outside traditionally recognized Mediterranean coastal regions. Furthermore, the failure of syndromic panel testing to detect HSV-1 and VZV highlights the need for complementary diagnostic strategies when clinical suspicion remains high. Overall, the detection of unexpected viral sequences, together with missed clinically actionable infections, supports the use of complementary molecular testing in selected cases of unexplained CNS syndromes when routine diagnostics are negative. These findings highlight the added diagnostic value of vmNGS and provide sequence-level data for future studies of viral diversity and molecular epidemiology in neurological disease.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 7","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13379243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Probing the sequence constraints for the stable incorporation of chimeric NSP1 segments into infectious rotaviruses.","authors":"Joseph Kendra, Gabriel I Parra","doi":"10.1099/jgv.0.002275","DOIUrl":"10.1099/jgv.0.002275","url":null,"abstract":"<p><p>Rotaviruses are a global cause of acute paediatric gastroenteritis. They present a genome of 11 dsRNA segments that have been successfully incorporated into a plasmid-based reverse-genetics system that enables the generation of reassortant and chimeric viruses as a possible foundation for multi-virus vaccines. Studies have shown that these chimeric segments are pruned across successive passages, highlighting a need to better define the constraints that govern segment recognition and stable incorporation into mature viruses. This work leveraged the reverse-genetics system to investigate these constraints by introducing a series of modifications to a chimeric NSP1 sequence with an internally cloned GFP insert (NSP1gfp). Across ten serial passages, a pruned NSP1gfp segment emerged and eventually outcompeted the original construct, resulting in a loss of GFP expression. The removal of the entire NSP1 ORF sequence 3' of the insert resulted in prolonged GFP expression, but closer examination of rotavirus RNA suggested that these modifications were merely delaying replacement from pruned segments, rather than avoiding their emergence. A series of systematic truncations to the remaining NSP1 ORF sequence 5' of the GFP insert showed that as little as 27 nt of the original coding sequence is needed for rescue of infectious chimeric rotavirus. Despite a near-total replacement of NSP1 with GFP, pruned segments emerged and were preferentially incorporated into later passages, which was correlated with increased infectivity at the expense of GFP expression. These results suggest that factors beyond excess segment size drive pruning of chimeric sequences. Closer sequence analysis of pruned segments revealed that pruning occurred at high GC regions of the insert, suggesting an inherent incompatibility with the genome composition of rotavirus segments. These findings shed light on the requirements for rotavirus segment recognition and stability, as well as provide important considerations for the usage of this model as a potential vaccine platform.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 7","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13338669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148375901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of influenza virus and coronavirus tropism, replication competence and disease severity in <i>ex vivo</i> and <i>in vitro</i> cultures of the human respiratory tract.","authors":"Denise I T Kuok, Angel P Y Ma, Rachel H H Ching, Ka Chun Ng, Jae W Lee, Michael A Matthay, Yi Guan, John M Nicholls, Leo L M Poon, J S Malik Peiris, Kenrie P Y Hui, Michael C W Chan","doi":"10.1099/jgv.0.002281","DOIUrl":"10.1099/jgv.0.002281","url":null,"abstract":"<p><p>The emergence of animal influenza viruses circulating in poultry and human populations poses a significant public health threat, yet current risk assessment tools that connect surveillance data to human transmission risk and disease severity are lacking. To address this, we employed a semi-quantitative approach to analyze virus tropism and replication competence, conducting risk assessments of influenza and coronavirus adaptation to human transmission in an <i>ex vivo</i> model, and evaluating virus-induced impairment of alveolar fluid clearance (AFC) <i>in vitro</i> as a correlation of disease severity. Our results showed that seasonal influenza A H1N1, H3N2, influenza B, MERS-CoV, and SARS-CoV exhibited productive viral replication and tissue infection in bronchial tissues, whereas wild bird surveillance isolates such as H5N3 and H7N1 showed minimal replication when compared to pandemic H1N1 and highly pathogenic avian influenza (HPAI) H5N1. Notably, differential lung viral replication and tissue tropism were detected for H5N6 and H9N2. HPAI H5N1, H7N9, MERS-CoV, and SARS-CoV caused more severe AFC impairment than seasonal H1N1, H3N2, and influenza B viruses, correlating with their clinical severity. Overall, these findings revealed an important association between viral tropism and human transmissibility in <i>ex vivo</i> explants, as well as the impairment of AFC <i>in vitro</i>, which aligns with the clinical manifestations of disease severity across different viral strains.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 7","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13331291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148375926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}