Journal of General Virology最新文献

{"title":"Core protein mutations are key determinants of hepatitis B virus replication during the hepatitis B e antigen-negative stage.","authors":"Diego Flichman, María Cecilia García, Hugo Norberto Granchetti, Rodolfo Campos, María Mercedes Elizalde","doi":"10.1099/jgv.0.002303","DOIUrl":"10.1099/jgv.0.002303","url":null,"abstract":"<p><p>The natural history of chronic hepatitis B virus (HBV) infection comprises distinct stages resulting from virus-host interactions. A late and pivotal event in this process is hepatitis B e antigen (HBeAg) seroconversion, marked by the abrogation of HBeAg expression, a significant reduction in viral load and the accumulation of mutations throughout the genome, particularly within the Core region. While HBeAg loss is associated with mutations in the basal core promoter and preCore regions, these alone do not account for the decreased viral load observed during this stage. To elucidate the contribution of Core variability to HBV replicative capacity, we engineered replication-competent chimeric genomes by reciprocally exchanging the core gene between a WT clone and three HBeAg-negative patient-derived isolates. These constructs were functionally characterized in Huh-7 cells to assess replication intermediates, antigen expression and viral transcriptional activity. Our findings demonstrate that mutations within the Core protein can either impair or enhance HBV replication, depending on their specific mutational patterns. Importantly, all viral replication intermediates were restored to WT levels when the WT Core protein was introduced into the HBeAg-negative genomes. Strong positive correlations between covalently closed circular DNA (CCC DNA) and other viral markers indicate that the Core protein exerts its regulatory effect primarily through regulation of CCC DNA levels. Notably, the absence of Core expression increased CCC DNA transcriptional activity, supporting a repressive role of the WT Core protein in gene expression. Collectively, these findings highlight the pivotal regulatory role of Core protein mutations in modulating HBV replication dynamics and gene expression during the HBeAg-negative phase and underscore its potential as a promising target for novel antiviral strategies.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 9","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13544899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891830","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":"Langerhans cells as targets of rabies virus immune evasion.","authors":"Keshia Kroh, Leanne C Helgers, Teunis B H Geijtenbeek, Carmen W E Embregts, Corine H GeurtsvanKessel","doi":"10.1099/jgv.0.002318","DOIUrl":"10.1099/jgv.0.002318","url":null,"abstract":"<p><p>Rabies virus (RABV) is a neurotropic virus of the genus <i>Lyssavirus</i> that causes a nearly always fatal encephalitis in humans once it reaches the central nervous system. Dog bites are a major transmission route of RABV, and following superficial skin exposure, RABV first encounters epidermal Langerhans cells (LCs), yet their role in early infection remains poorly understood. Here, we show that exposure of immature human epidermal LCs to RABV leads to RABV association with cells in the absence of productive viral replication. RABV-exposed LCs display reduced cytokine and type I IFN responses and lack induction of IFN-stimulated genes, indicating suppression of antiviral signalling pathways. Together, these findings suggest that RABV is efficiently taken up by immature LCs, which dampens the antiviral immune responses of LCs, potentially facilitating immune evasion at the skin entry site.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 9","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13585407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148989358","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>Bacilladnaviridae</i> 2026.","authors":"Arvind Varsani, Yuji Tomaru, Kenta Okamoto, Anna Munke, Mart Krupovic","doi":"10.1099/jgv.0.002321","DOIUrl":"10.1099/jgv.0.002321","url":null,"abstract":"<p><p><i>Bacilladnaviridae</i> is a family of viruses with single-stranded, circular DNA genomes that range from 3.4 to 6 kb and contain a short double-stranded region of 0.5-1 kb. The genome is replicated by the rolling-circle mechanism. Bacilladnavirids encode a jelly-roll capsid protein which forms non-enveloped icosahedral capsids with a <i>T</i>=3 symmetry. All cultured bacilladnavirids infect diatoms, a group of unicellular algae (Stramenopiles), and cause lysis of the host cells. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family <i>Bacilladnaviridae</i>, which is available at ictv.global/report/bacilladnaviridae.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 9","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13623192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081043","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":"A two-step processing method is recommended to inactivate human sporadic M1 and V2 prions.","authors":"Shirou Mohri, Yuichi Matsuura, Piero Parchi, Tetsuyuki Kitamoto","doi":"10.1099/jgv.0.002326","DOIUrl":"10.1099/jgv.0.002326","url":null,"abstract":"<p><p>Most human-acquired prion diseases result from infection with M1 or V2 prions from sporadic Creutzfeldt-Jakob disease. To prevent transmission via surgical instruments, sterilization methods targeting these prions are essential. In this study, stainless steel wires coated with M1 or V2 prions were used to evaluate inactivation protocols. None of the individual treatments - autoclaving, SDS or NaOH - eliminated infectivity except for autoclaving against V2 prions. Autoclaving at 134 °C revealed distinct thermal stability between M1 and V2, with M1 exhibiting greater thermal stability. Importantly, combining methods, which we herein called two-step processing methods, achieved practical inactivation: SDS treatment followed by autoclaving at 121 °C was highly effective. Commercial alkaline detergents also proved effective against M1 prion under a combination of high pH and temperature. The inability to detect infection in our model mice using our assay system demonstrates that the infectivity titre decreased to 10⁻⁸ in M1 and 10⁻⁷ in V2. These findings indicate that synergistic approaches can achieve prion inactivation under practical conditions, supporting the need for revised sterilization protocols to prevent iatrogenic transmission.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 9","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13581090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148983006","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":"A naturally occurring feline leukaemia virus subgroup A variant exhibits broad mammalian cellular tropism and utilizes canine thiamine transporter 1.","authors":"Yuka Kanemura, So Nakagawa, Takayuki Miyazawa","doi":"10.1099/jgv.0.002316","DOIUrl":"10.1099/jgv.0.002316","url":null,"abstract":"<p><p>Feline leukaemia virus subgroup A (FeLV-A) has generally been regarded as having a narrow, predominantly feline host range. Here, we characterize a naturally occurring FeLV-A isolate, strain F8701, that exhibits unexpectedly broad mammalian cell tropism. Using an infectious molecular clone of F8701, we show that F8701 infects canine cells efficiently and can utilize the canine orthologue of thiamine transporter 1, the canonical FeLV-A receptor. Compared with reference FeLV-A strains, F8701 displayed markedly higher infectivity in multiple non-feline cell lines, including canine and human cells. Sequence analysis of the envelope glycoprotein revealed that F8701 carries the previously described 83D/91D di-aspartic acid residue combination in variable region A, together with an additional K105N substitution whose functional contribution remains to be determined. Interference assays confirmed that F8701 belongs to FeLV subgroup A, indicating that broad cellular tropism can occur within a naturally occurring FeLV-A background. Although replication in cultured canine cells was observed, whether F8701 can establish productive infection or transmission in dogs <i>in vivo</i> remains unknown. These findings highlight the natural plasticity of the FeLV-A envelope and suggest that receptor compatibility can contribute to the expansion of mammalian cellular tropism, while additional host-level barriers are likely to determine cross-species infection <i>in vivo</i>.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 9","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13623193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081083","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":"Evaluation of the contribution of the minor envelope complex glycoprotein 3 ectodomain to the porcine reproductive and respiratory syndrome virus 1 neutralizing antibody response.","authors":"Jack W P Hayes, Jane C Edwards, Kristel Ramirez Valdez, Sylvia Crossley, Rory C F de Brito, Danish Munir, Kevan Hanson, Kostas Paschos, Krunal Polra, Jeongho An, Jay G Calvert, Marie Bonnet Di Placido, Jonathan F Lovell, Robin Shattock, John A Hammond, Raymond J Owens, Simon P Graham","doi":"10.1099/jgv.0.002328","DOIUrl":"10.1099/jgv.0.002328","url":null,"abstract":"<p><p>Porcine reproductive and respiratory syndrome viruses (PRRSVs) cause significant economic losses to the global swine industry. Current live attenuated vaccines are unable to effectively control PRRSV infection, and strain variability, driven by rapid mutation, complicates the development of improved vaccines. Identification of the targets of broadly neutralizing antibodies is crucial for guiding next-generation vaccine design, yet PRRSV glycoproteins bearing conserved neutralizing epitopes remain poorly defined. To address this, recombinant soluble forms of PRRSV-1 envelope glycoproteins, GP2, GP3 and GP4, were produced using mammalian cells. The screening of serum from hyperimmune pigs demonstrated GP3 as the most highly recognized of the three glycoproteins. Fluorescently tagged GP3-tetramers were utilized to isolate single B cells from a hyperimmune pig via flow cytometry. Immunoglobulin VH and VL regions were amplified by RT-PCR and sequenced. Fifteen unique heavy and light chain pairs were cloned and expressed as recombinant monoclonal antibodies (mAbs). mAbs were evaluated for specificity, cross-reactivity and neutralizing capacity. Antigenic sites targeted by GP3-specific mAbs were mapped to several conserved linear sequences, but mAbs did not exhibit virus neutralizing activity <i>in vitro</i>, suggesting that these may serve as decoy epitopes. An immunogenicity study with recombinant GP3, delivered as a protein subunit or via an RNA vector, also demonstrated a lack of neutralizing antibody response despite high GP3-binding antibody titres. Collectively, these data suggest that antibodies directed against the isolated PRRSV-1 GP3 ectodomain are unlikely to contribute substantially to neutralization. However, the workflow established for isolating porcine mAbs could be utilized in future research to further dissect the neutralizing antibody response to PRRSV.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 9","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13541077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887676","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":"Enhanced recovery of terminal sequences of viral RNAs via fine-tuning of the high-throughput sequencing library preparation and evidence of a non-templated nucleotide addition at the 3' end of the minus strand in members of the genus <i>Ilarvirus</i>.","authors":"Dennis Knierim, Paolo Margaria","doi":"10.1099/jgv.0.002331","DOIUrl":"10.1099/jgv.0.002331","url":null,"abstract":"<p><p>High-throughput sequencing (HTS) technologies have transformed life sciences by enabling rapid, large-scale analysis of nucleic acids, providing unprecedented insights into genomics and transcriptomics. Accurate determination of RNA termini remains, however, a major challenge. We have addressed this limitation by fine-tuning a commercial HTS library preparation protocol. The optimized strategy was validated on plant virus isolates representing diverse taxonomic groups and genome architectures and benchmarked against conventional RACE, demonstrating its effectiveness and robustness. Investigations in members of the genus <i>Ilarvirus</i> allowed to prove the occurrence of non-templated nucleotide additions at the 3' end of the minus-strand viral RNAs <i>in vivo</i>, expanding previous results obtained <i>in vitro</i> in related members in the <i>Bromoviridae</i> and supporting that this feature may be common across the family.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 9","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13541289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887653","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 mammary tissues are susceptible to infection by viruses bearing panzootic H5N1 influenza A virus glycoproteins.","authors":"Rebecca A Ross, Sarah K Walsh, Hannah Montgomery, Hanting Chen, Edward Hutchinson, Pablo R Murcia","doi":"10.1099/jgv.0.002338","DOIUrl":"10.1099/jgv.0.002338","url":null,"abstract":"<p><p>The emergence of the panzootic clade 2.3.4.4b highly pathogenic H5N1 avian influenza in 2020 marked a major expansion in the host range of influenza A viruses (IAVs), raising concerns about further cross-species transmission events and zoonotic spillover. The introduction of 2.3.4.4b viruses into US dairy herds has resulted in widespread circulation, accompanied by reduced milk yield, mastitis and high viral loads in milk. Notably, virus circulation in dairy cattle represents a novel route for mammalian adaptation and transmission that has already led to more than 40 human cases in the USA since 2024. As haemagglutinin (HA) is the primary determinant of viral host range and tissue tropism, we investigated whether viruses containing the glycoproteins of avian H5N1 subclade 2.3.4.4b viruses could infect mammary tissue from Aberdeen Angus, Holstein Friesian and Limousin cattle. Using mammary gland explants, we inoculated tissues with attenuated reassortant viruses expressing the HA and neuraminidase (NA) of three 2.3.4.4b viruses that predated the emergence of H5N1 in the US cattle: A/chicken/England/053052/2021 (AIV07), A/chicken/Scotland/054477/2021 (AIV09) and A/chicken/England/085598/2022 (AIV48). Detection of viral NP antigen by immunohistochemistry in explants from both the teat and gland cistern for all three breeds following inoculation with AIV09 and AIV48 indicates that mammary tissue from each of the three tested cattle breeds is susceptible to infection by viruses bearing H5N1 glycoproteins. Lectin staining showed expression of both α2,3- and α2,6-linked sialic acids in the mammary tissue of all donors, indicating that all three breeds have the potential to support infection with both avian- and mammalian-adapted IAVs. Together, these findings demonstrate that the mammary glands from both beef and dairy cattle breeds are susceptible to infection with viruses bearing avian-origin H5N1 glycoproteins and suggest that bovine mammary tissue may provide an environment in which diverse IAVs could co-infect the same tissue. This possibility underscores the need for further investigation and the inclusion of both beef and dairy cattle in ongoing H5N1 surveillance and risk-assessment frameworks.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 9","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13581240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148982221","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":"Genomic characterization of Lao <i>Mobatvirus</i> strains reveals host-associated clustering in Southeast Asian bats.","authors":"Chittaphone Vanhnollat, Kristina Dimitrova, Longthor Vachouaxiong, Jonathan Audet, Somphavanh Somlor, Sarah J Medina, Phaithong Bounmany, Khaithong Lakeomany, Vaekey Vungkyly, Gary Wong, Vilakhan Xayaphet, Phetphoumin Paphaphanh, Watthana Theppangna, Bounsavane Douangboubpha, Khamsing Vongphayloth, David Safronetz, Philippe Buchy","doi":"10.1099/jgv.0.002333","DOIUrl":"10.1099/jgv.0.002333","url":null,"abstract":"<p><p>While members of the genus <i>Orthohantavirus</i> are well-established human pathogens, the zoonotic potential of bat-associated hantavirids, particularly those within the genus <i>Mobatvirus</i>, remains largely unresolved. To investigate the genetic diversity of these lineages in Southeast Asia, we conducted an expanded surveillance programme in Lao PDR from May 2023 to October 2025 in bat populations and wild animals from local wet markets. Using molecular screening and deep sequencing to characterize hantavirids from bat populations and wild animals from local wet markets, we identified 20 positive samples across four bat species, recovering coding-complete genomes for multiple novel variants. Phylogenetic analysis confirmed that these viruses clustered within <i>Mobatvirus</i>, resolving into two major subclades. The first subclade clustered with Quezon and Robina viruses found in fruit-eating bats. The second subclade further split into two lineages corresponding to Ðakrông and Xuân Sơn viruses, which are associated with trident and leaf-nosed bats, respectively. Despite the strong host association observed, the detection of these viruses in a wet market highlights this setting as a potential human exposure interface. These findings significantly expand the known diversity of mobatviruses in Laos and highlight the urgent need for serological surveillance in at-risk human populations to assess the potential for spillover.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 9","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13557741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148919941","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":"Amino acid homorepeats in tape measure proteins correlate with bacteriophage tail length.","authors":"Antonio Moreno-Rodríguez, Antonio J Pérez-Pulido, Pablo Mier","doi":"10.1099/jgv.0.002341","DOIUrl":"10.1099/jgv.0.002341","url":null,"abstract":"<p><p>The tape measure protein (TMP) dictates the tail length of tailed bacteriophages. However, the sequence features that drive the process of length fine-tuning have not yet been described. Tandem repeats (TRs), stretches of aas organized as multiple adjacent copies of the same or very similar sequence motif, are contributors to TMP length variation. Homorepeats (polyX regions) are a specific type of TRs composed of stretches of identical aas, forming low-complexity regions that contribute to protein structural flexibility and dynamics. Here, we performed a large-scale analysis of polyX regions across 12 million phage proteins to test whether these homorepeats help explain the variable length of flexible phage tails. PolyX tracts were detected in 41% of all phage proteins and in 95.5% of TMPs, with polyA, polyG, polyS and polyT dominating the composition. Furthermore, the number of polyX tracts in TMPs scaled directly with protein length. About half of the TMPs have both polyX and TRs (23,469 out of 45,500 TMPs), but nearly half of the polyX-containing TMPs lacked any TRs (19,999 out of 43,468 TMPs), showing that polyX are independent features rather than by-products of larger repeats. Morphological comparisons showed that phages with long and flexible tails (Siphovirus morphotype) combine polyX and TRs, whereas shorter or contractile-tailed phages rely mostly on polyX. Last, the total aa content in polyX regions correlated significantly with experimentally measured tail lengths (<i>R</i>²=0.811, <i>P</i>=1.56×10^-⁴). Our results identify polyX tracts as an important and tunable component of TMPs that enable precise control of phage tail length.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 9","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13585406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148990217","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}