Journal of General Virology最新文献

{"title":"A solinvivirus induces cellular antiviral responses and reduces the lifespan of adult black soldier flies.","authors":"Robert D Pienaar, Pablo García-Castillo, Harmony Piterois, Violette Wallart, Frédéric Manas, Elisabeth A Herniou, Salvador Herrero","doi":"10.1099/jgv.0.002234","DOIUrl":"10.1099/jgv.0.002234","url":null,"abstract":"<p><p>Viral pathogens pose an emerging threat to the sustainability of insect mass-rearing systems, yet they remain understudied in key species like the black soldier fly (BSF; <i>Hermetia illucens</i>). Although multiple viral sequences have been reported in BSF, their role in disease has not been established until now. Here, we provide the first <i>in vivo</i> characterization of <i>H. illucens</i> solinvivirus (HiSvV), confirming its role as a viral entomopathogen of BSF. Metatranscriptomic analysis of a diseased colony revealed a high viral load attributable to HiSvV. We successfully isolated the virus and developed injection- and oral-based infection assays to investigate replication, tissue tropism, transmission and risk of mortality. HiSvV replicated in inoculated adults, induced premature mortality in flies and was transmitted both horizontally and vertically. Infected flies also mounted a broad antiviral response, which supported active pathogenesis, even if the small RNA pathways were not activated. These findings establish HiSvV as the first confirmed viral pathogen of BSF and underscore the urgent need for viral surveillance and experimental tools to safeguard industrial insect rearing.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12952803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147326366","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":"Optimization of lytic herpes simplex virus infection in human induced pluripotent stem cell-derived cortical neurones.","authors":"Daniel A Nash, Alex S Nicholson, Henry G Barrow, Viv Connor, Colin M Crump, Janet E Deane, Stephen C Graham","doi":"10.1099/jgv.0.002237","DOIUrl":"10.1099/jgv.0.002237","url":null,"abstract":"<p><p>Herpes simplex virus (HSV)-1 infection of cortical neurones is a leading cause of encephalitis. Whilst we have substantial knowledge about the molecular virology of HSV-1 lytic infection in cells of the periphery, like keratinocytes or fibroblasts, we know much less about infection of human neurones owing to the challenges of working with neuronal cell-based models. Here, we demonstrate the use of a human induced pluripotent stem cell-derived cortical neurone model (i3Neurones) for HSV-1 infection. i3Neurones are highly scalable and can be rapidly and efficiently differentiated into an isogenic population of cortical glutamatergic neurones. We show that i3Neurones support the full HSV-1 lytic replication cycle. We present an optimized protocol for the infection of i3Neurones with HSV-1 that allows their synchronous infection at near-100% efficiency and optimized fixation methods that preserve organelle and neurite structure for immunocytochemistry analysis. Our study highlights i3Neurones as a robust, scalable platform for microscopy and biochemical studies of HSV-1 and other neurotropic pathogens.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12952538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147326343","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":"Integrating metagenomics and metatranscriptomics into <i>Orthoflavivirus</i> diagnosis: a transformative approach for clinical virology.","authors":"Md Eram Hosen, Paul F Horwood, Subir Sarker","doi":"10.1099/jgv.0.002247","DOIUrl":"10.1099/jgv.0.002247","url":null,"abstract":"<p><p>Diagnostic inaccuracies are a major yet often overlooked threat to global health, leading to delayed treatment, preventable harm and systemic gaps in disease control. Among the most affected domains are <i>Orthoflavivirus</i> infections, which pose ongoing diagnostic challenges due to antigenic cross-reactivity, overlapping clinical symptoms and the narrow temporal sensitivity of standard tools such as serology and reverse transcription polymerase chain reaction. These constraints have led to widespread misdiagnoses and underreporting, ultimately hampering both effective clinical management and public health response. Recent advances in metagenomic and metatranscriptomic sequencing offer a transformative solution by enabling unbiased, simultaneous pathogen detection and real-time profiling of viral and host transcriptomics. In this review, we assess the diagnostic performance and translational value of these approaches in resolving <i>Orthoflavivirus</i> infections, with case examples from clinical settings in countries like the USA, UK, China and Germany which have already implemented these approaches into routine diagnosis in some settings. We examine key methodological considerations, including optimal sample timing, sample types and processing, sequencing strategy selection and the diagnostic performance of various platforms. We highlight the growing use of metatranscriptomics for detecting active infections, profiling viral and host responses, identifying coinfections and supporting real-time surveillance. We also discuss the key challenges such as technical expertise, lack of standardization, cost, turnaround time and regulatory approval that currently limit global implementation. Finally, we highlight emerging international efforts to integrate sequencing-based diagnostics into routine hospital workflows. Together, these innovations mark a critical shift toward precision diagnostics for <i>Orthoflavivirus</i> infections, with broad implications for clinical settings.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13035173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147574280","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 respiratory syncytial virus utilizes the human insulin-like growth factor 1 receptor in the late stages of infection.","authors":"Sodbayasgalan Amarbayasgalan, Tatsuki Takahashi, Yoshiro Sugiura, Kenta Shimizu, Enkhjin Dorjsuren, Like Luo, Wataru Kamitani","doi":"10.1099/jgv.0.002241","DOIUrl":"10.1099/jgv.0.002241","url":null,"abstract":"<p><p>Bovine respiratory syncytial virus (BRSV) is a major viral pathogen associated with the bovine respiratory disease complex, which is a leading cause of morbidity, mortality and economic loss in the cattle industry worldwide. Clinical infection is most severe in young calves, where it commonly causes lower respiratory tract inflammation, bronchopneumonia and predisposition to secondary bacterial infections. In experimental research, BRSV is typically maintained in Vero and MDBK cells. Although reverse genetics systems have been established for BRSV, we developed a bacterial artificial chromosome-based reverse genetics system for the virus. We successfully recovered a recombinant BRSV with the ZsGreen reporter gene inserted between the P and M genes. The recombinant virus displayed comparable growth kinetics to the WT strain, demonstrating the utility of the system for generating reporter viruses. Reporter virus infectivity assessments in mammalian MDBK, VeroE6, HEp-2 and HEK293T cells revealed that HEK293T cells are permissive to BRSV. To investigate the potential role of human insulin-like growth factor 1 receptor (hIGF1R), which human RSV uses for entry, we infected insulin-like growth factor 1 receptor (IGF1R)-knockout (KO) 293 T cells with BRSV-ZsGreen. At 24 h post-infection (hpi), ZsGreen levels were similar between WT and hIGF1R-KO cells; however, by 72 hpi, viral spread was markedly reduced in hIGF1R-KO cells and correlated with IGF1R levels. These findings suggest that IGF1R is dispensable for early BRSV infection but contributes to efficient viral propagation in later stages.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13016481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147512700","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":"In vivo inhibition of JAK-STAT signalling enhances high pathogenicity influenza virus replication in ducks.","authors":"Juliette Gross, Bertille Pouget, Margot Sarrat, Charlotte Foret-Lucas, Sébastien Mathieu Soubies, Céline Bleuart, Nicolas Gaide, Romain Volmer, Pierre Bessière","doi":"10.1099/jgv.0.002238","DOIUrl":"10.1099/jgv.0.002238","url":null,"abstract":"<p><p>While rapid death is the usual outcome of high pathogenicity avian influenza virus (HPAIV) infection in gallinaceous poultry, HPAIV-infected ducks usually present milder clinical signs and shed virus for a prolonged time. The difference in disease severity has been linked to a more rapid type I IFN immune response and reduced proinflammatory cytokine expression in ducks compared to chickens. To investigate the role of the early antiviral innate immune response in controlling viral replication in ducks, we evaluated the effects of ruxolitinib, a Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway inhibitor known to dampen IFN signalling in mammals. We first optimized a treatment protocol in 2-week-old ducklings and showed that repeated intracoelomic injections of ruxolitinib significantly decreased IFN-stimulated gene (ISG) mRNA levels in the lung, while oral administration was ineffective. In subsequent infection experiments with an H5N9 HPAIV strain, ruxolitinib treatment led to an earlier peak of viral shedding and increased viral RNA levels in respiratory tissues, which however was not associated with increased expression of clinical signs. Analysis of host immune gene expression in the respiratory tract confirmed a transient suppression of ISG expression coincident with ruxolitinib treatment, followed by a recovery once treatment was ceased. This work provides the first demonstration of the effectiveness of ruxolitinib at inhibiting the antiviral innate immune response in birds, causing increased levels of virus replication when administered to HPAIV-infected ducks.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12952537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147326333","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":"Immunogenicity of SARS-CoV-2 vaccine prototype based on virus-like particles of hepatitis B core antigen from genotype G and interleukin 12 expressing Semliki Forest virus as a genetic adjuvant.","authors":"Andris Dislers, Olga Nilova, Juris Jansons, Dace Skrastina, Janis Bogans, Ivars Petrovskis, Karina Spunde, Rolans Stepanovs, Andris Kazaks, Anna Zajakina, Irina Sominskaya","doi":"10.1099/jgv.0.002240","DOIUrl":"10.1099/jgv.0.002240","url":null,"abstract":"<p><p>Virus-like particles (VLPs) based on hepatitis B core antigen (HBc) represent an immunogenic and modular platform for epitope presentation. In this study, the VLPs formed by the modified recombinant hepatitis B core antigen from genotype G (HBc/G) were used as carriers for the presentation of a receptor-binding motif (RBM) of the Delta variant of Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2). The RBM was inserted at the C-terminus of the modified HBc/G extended by the addition of a second, specifically modified C-terminal domain of HBc/G. All arginine residues in the extra domain were replaced with glycine, resulting in a 'two-tailed' HBc/G-Gly vector. The resulting HBc/G-Gly-RBM construct successfully formed regular VLPs in <i>Escherichia coli</i> and elicited specific antibody responses in mice. Despite the moderate immunogenicity of the RBM insert compared with the HBc carrier, sera from RBM-VLP-immunized animals exhibited neutralizing activity against MLV particles pseudotyped with the SARS-CoV-2 Delta spike and showed cross-reactivity with receptor-binding domains from the Wuhan and Omicron variants. To enhance the immune response, a replication-deficient Semliki Forest virus (SFV) vector expressing IL-12 was evaluated alone and in combination with the squalene-based adjuvant AddaVax. The co-administration of SFV-IL12 and AddaVax modestly improved virus neutralization rates and promoted a Th1 response, characterized by increased IgG2a production and IFN-<i>γ</i> secretion. These findings demonstrate the feasibility of combining classical and genetic adjuvants with the HBc-based VLP platform and provide preliminary insights for further optimization toward more potent and protective SARS-CoV-2 vaccine candidates.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12962599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147355366","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":"Multiple origins and functions: evolutionary pathways of HSP70 proteins in viruses.","authors":"Ayoub Maachi, Santiago F Elena","doi":"10.1099/jgv.0.002242","DOIUrl":"10.1099/jgv.0.002242","url":null,"abstract":"<p><p>Heat shock protein 70s (HSP70s) are highly conserved molecular chaperones found across all domains of life, where they play essential roles in cellular stress responses. Whilst HSP70 homologues have been previously identified in closteroviruses that have ssRNA genomes, their broader presence and evolutionary history in viruses remain poorly understood. In this study, we conducted a comprehensive search of viral protein databases and identified HSP70 homologues in viruses beyond those with ssRNA genomes, including examples with dsDNA genomes in the class <i>Megaviricete</i>. These viral HSP70s exhibit diverse gene organizations, copy numbers and structural features. Notably, HSP70s of viruses from <i>Megaviricetes</i> showed up to three gene copies per genome and distinct structural motifs, whilst those from closteroviruses displayed higher sequence and structural diversity, suggesting faster evolutionary rates. Structural and phylogenetic analyses revealed two major clusters of viral HSP70s, with dsDNA virus HSP70s closely resembling those of their protist hosts, supporting the hypothesis of horizontal gene transfer. In contrast, ssRNA virus HSP70s formed a distinct, highly divergent group. Our findings suggest multiple independent acquisitions of HSP70 genes by viruses and provide new insights into their evolutionary trajectories and potential functional adaptations.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12978162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147433420","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":"Decoding the antiviral potential of eugenol, thymol and vanillin against human cytomegalovirus infection.","authors":"Clara Martín-Martín, María Ruiz-Rico, José Manuel Barat, Estéfani García-Ríos, Pilar Pérez-Romero","doi":"10.1099/jgv.0.002248","DOIUrl":"10.1099/jgv.0.002248","url":null,"abstract":"<p><p>Human cytomegalovirus (HCMV) poses serious health risks, particularly for immunocompromised individuals. However, the current FDA-approved anti-HCMV drugs face challenges such as drug resistance and significant side effects, underscoring the need for alternative treatment options. Essential oil components (EOCs), including eugenol, thymol and vanillin, are recognized for their therapeutic potential. This study evaluates their antiviral effects against HCMV in epithelial (ARPE-19) and fibroblast (MRC-5) cell lines. Among the EOCs, vanillin demonstrated the highest efficacy, characterized by low toxicity and a high selectivity index in both cell types. Mechanistic differences were noted between the cell lines. In ARPE-19 cells, eugenol showed virucidal activity, inhibited viral entry and suppressed early gene expression (IE-1). Conversely, in MRC-5 cells, eugenol mainly blocked viral entry and exhibited virucidal effects. Thymol was most effective in ARPE-19 cells, where it completely suppressed IE-1 expression as a result of both inhibition of viral entry and a direct disruptive effect on IE-1 expression. In addition, thymol showed an effect on viral replication. In MRC-5 cells, thymol primarily inhibited viral entry and attachment. Vanillin exhibited dual inhibitory activity in both cell lines, blocking viral attachment and entry. In MRC-5, vanillin also appears to affect intermediate processes. Notably, combining EOCs with ganciclovir resulted in synergistic effects. The eugenol/ganciclovir combination was particularly effective in ARPE-19 cells, while thymol/ganciclovir showed enhanced efficacy in MRC-5 cells. These findings suggest that EOCs have significant potential as adjunct therapies to improve antiviral outcomes and address drug-resistant HCMV strains.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12999277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147481089","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":"SARS-CoV-2 Nsp15 facilitates immune evasion and viral replication by limiting multiple host innate immune pathways, including cGAS-STING.","authors":"Hsin-Ping Chiu, Yao Yu Yeo, Tsoi Ying Lai, Chuan-Tien Hung, Shreyas Kowdle, Griffin D Haas, Sizun Jiang, Weina Sun, Benhur Lee","doi":"10.1099/jgv.0.002233","DOIUrl":"10.1099/jgv.0.002233","url":null,"abstract":"<p><p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nonstructural protein 15 (Nsp15) is a conserved uridine-specific endoribonuclease (EndoU) and is implicated in innate immune evasion, yet its precise molecular mechanism remains incompletely understood. Here, we demonstrate that Nsp15 limits antiviral innate immune responses in part by downregulating the cGAS-STING pathway. To investigate how Nsp15 antagonizes host innate immune responses, we engineered recombinant SARS-CoV-2 bearing WT or EndoU-inactive Nsp15 (H234A). Compared with the WT virus, the Nsp15-H234A mutant exhibited a 2-log decrease in peak viral titres in interferon (IFN)-competent A549-ACE2 cells, but not in their STAT1 knockout counterparts. This attenuation was partially reversed by STING knockout or STING inhibitors, highlighting STING's involvement in Nsp15-driven immune evasion. Transcriptomic analyses revealed the upregulation of IFNs and IFN-stimulated genes in cells infected with the Nsp15-H234A mutant virus. Notably, cGAS and STING transcripts and proteins were suppressed during WT but not mutant virus infections - even in STAT1-deficient cells - suggesting that Nsp15 contributes directly to their downregulation. <i>In vitro</i>, Nsp15 targeted cGAS and STING transcripts in an EndoU activity-dependent manner, thereby reducing cGAS-STING-driven IFN-<i>β</i> and NF-<i>κ</i>B reporter activation. Infection of Syrian hamsters confirmed that the Nsp15-H234A mutant virus replicated to lower titres in respiratory tissues and elicited stronger expression of innate immune-related genes. Collectively, these findings define a key strategy by which SARS-CoV-2 Nsp15 subverts the cGAS-STING pathway to facilitate viral replication and immune evasion and underscore Nsp15 EndoU activity as a potential target for future coronavirus antiviral or vaccine design.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13016584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147512691","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":"Knockout of key receptors (PDGFRA and NRP2) in the guinea pig model blocks direct and endocytic pathways of CMV cell entry.","authors":"Yushu Qin, K Yeon Choi, Nadia El-Hamdi, Alistair McGregor","doi":"10.1099/jgv.0.002236","DOIUrl":"10.1099/jgv.0.002236","url":null,"abstract":"<p><p>The guinea pig with guinea pig cytomegalovirus (GPCMV) is the only small-animal model for congenital cytomegalovirus, a leading cause of cognitive impairment and hearing loss in newborns. GPCMV encodes human cytomegalovirus (HCMV) homologues of viral entry glycoprotein complexes, which are neutralizing-antibody vaccine targets. As with HCMV, GPCMV has two pathways of cell entry (direct and endocytic). Specific viral gH/gL-based complexes are necessary for receptor interaction and cell entry: gH/gL/gO trimer (direct) and pentamer complex (PC) (endocytic). Both pathways also require gB as the fusogenic protein. Direct GPCMV cell entry requires platelet-derived growth factor receptor alpha (PDGFRA), but an endocytic PC receptor remains unknown. We hypothesized that cellular knockout of direct and endocytic receptors would completely block infection, which cannot be achieved by gB-based antibodies. Candidate receptors including neuropilin proteins (NRP1, NRP2) and CD147 present on all established guinea pig cell lines were selected based on importance as common virus receptors or in fetal development. Results demonstrated that NRP2 interacted with PC, unlike NRP1 or CD147, in immunoprecipitation assays and eliminated NRP1/NRP2 heterodimer receptor interaction. The viral trimer only interacted with PDGFRA. Double knockout of PDGFRA/NRP2 completely blocked GPCMV infection. In contrast, the CD147/PDGFRA double knockout had limited GPCMV inhibition, and the single knockout of CD147 had no impact. Knockout of the various receptors had no effect on control HSV-1 infection. Ectopic expression of guinea pig cell receptors restored GPCMV infection but not human NRP2/PDGFRA, indicating a basis for the species-specific barrier for GPCMV and HCMV infection. Overall, results increase the translational relevance of GPCMV for the development of CMV intervention strategies.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12978165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147433377","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}