Journal of General Virology最新文献

{"title":"Infectivity of recombinant Torque teno sus virus 1 in pigs coinfected with swine influenza virus.","authors":"Md-Tariqul Islam, Angela Pillatzki, Brett Webb, Sheela Ramamoorthy","doi":"10.1099/jgv.0.002264","DOIUrl":"10.1099/jgv.0.002264","url":null,"abstract":"<p><p>Torque teno viruses (TTVs) are small non-enveloped DNA viruses that are ubiquitous among mammalian species. Although their pathogenic potential remains uncertain, TTVs can modulate host immunity and potentiate coinfecting pathogens or comorbid conditions. Progress in understanding TTV biology has been constrained by the absence of robust <i>in vitro</i> and <i>in vivo</i> experimental systems. To address these limitations, we investigated the infectivity of a recombinant swine TTV [Torque teno sus virus 1 (TTSuV1)] generated with a reverse genetics system in a snatch-farrowed piglet model. Additionally, we evaluated the impact of TTSuV1 coinfection on the pathogenesis and replication dynamics of swine influenza virus (SIV). Infection of piglets with the rescued TTSuV1 induced seroconversion and lymphopenia. Early infection was associated with reduced lymphocyte proliferative responses to mitogens and diminished or absent recall responses to viral antigens. TTSuV1 antigen was detected within immune cell populations by flow cytometry. Contrary to expectations, prior TTSuV1 infection did not significantly exacerbate SIV-associated clinical signs or pulmonary lesions. The use of a snatch-farrowed piglet model in combination with recombinant TTSuV1 derived from reverse genetics provides a controlled system for investigating TTV-host interactions. This approach represents a valuable tool for advancing mechanistic studies of TTV biology and its role in modulating coinfections.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13151893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838809","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":"Benchmarks for taxonomic classification of jingmenviruses and closely related viruses using newly identified genomic sequences.","authors":"Agathe M G Colmant, Rhys H Parry, Remi Charrel, Bruno Coutard","doi":"10.1099/jgv.0.002254","DOIUrl":"10.1099/jgv.0.002254","url":null,"abstract":"<p><p>Jingmenviruses are a group of viruses related to orthoflaviviruses characterized by a segmented genome and multipartite organization that have been detected worldwide in a wide range of hosts. With the growing number of new jingmenvirus sequences identified in metagenomics data, it can be difficult to assess whether a new sequence is associated with a new virus species or with a strain of an existing species. The ICTV is about to ratify the reclassification of the <i>Flaviviridae</i> family, recognizing segmented viruses previously designated jingmenviruses as part of that family and proposing two genera to classify them: <i>Jingmenvirus</i> and <i>Guaicovirus</i>. These proposals do not include clear criteria to classify jingmenviruses and related sequences into species or genera. In order to determine such criteria, we generated a large sequence database from published and newly assembled sequences. Indeed, we screened public raw sequencing data from studies that did not search for or report jingmenvirus or related sequences, looking for new strains of previously described viruses. We then performed multiple sequence alignments and used the inferred percentage identity values to determine demarcation criteria based on the distribution of evolutionary distances upon pairwise comparisons. We report the identification of almost 60 libraries containing jingmenvirus and related sequences, in a wide range of sample types and geographical locations. Using these data and published sequences, we have determined that to be classified as a virus species, at least four segments are required, on which eight cut-off values in percentage identity (nucleotide and amino acid) are used for demarcation. The use of these criteria would enhance consistency in jingmenvirus taxonomy and provide a standardized framework for comparative genomics studies of these viruses, as they are still under-characterized.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13155725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838790","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 G57 (BJ/94-like) H9N2 avian influenza virus exhibits enhanced replication and tissue dissemination in chickens compared with a G1-B virus.","authors":"Sushant Bhat, Jean-Remy Sadeyen, Jiayun Yang, Klaudia Chrzastek, Thusitha K Karunarathna, Audra-Lynne Schlachter, Mehnaz Qureshi, Arslan Mehboob, Dagmara Bialy, Benjamin C Mollett, Alejandro Nunez, Holly Shelton, Munir Iqbal","doi":"10.1099/jgv.0.002259","DOIUrl":"https://doi.org/10.1099/jgv.0.002259","url":null,"abstract":"<p><p>Avian influenza H9N2 viruses cause economic losses to the poultry industry and pose a public health risk. Two major H9N2 lineages dominate globally: the G1 lineage (genotype G1-B), prevalent in the Middle East, Africa and South Asia, and the BJ/94 lineage (predominantly genotype G57), dominant in China, Vietnam, South Korea, Indonesia and the Far East. We investigated replication, transmission and pathogenicity of prototype strains from these two lineages to link genotype to phenotype. The G57 virus A/Ck/Vietnam/H7F-14-BN4-315/2014 (Vietnam/315) was more lethal and showed greater tissue dissemination in chicken embryos than the G1-B virus A/chicken/Pakistan/UDL-01/2008 (Pakistan/UDL-01). Vietnam/315 exhibited higher replication in directly infected and contact chickens, with increased oropharyngeal and cloacal shedding and tissue dissemination. In contrast, the Pakistan/UDL-01 virus was shed mainly from the oropharynx at lower levels and remained localized to nasal tissues and trachea, highlighting differences in replication, tissue tropism and transmission. Gene analysis showed that the matrix (M) gene of Vietnam/315 enhanced replication in primary chicken kidney cells, while polymerase basic 2 (PB2), haemagglutinin (HA), neuraminidase (NA) and M genes promoted increased replication in Madin-Darby canine kidney cells. Both viruses preferentially bound to sulphated avian-like receptors. However, Vietnam/315 showed higher NA activity and a more acid-stable HA (pH fusion 5.2) than Pakistan/UDL-01. These findings indicate that the G57 genotype strain examined exhibits greater replication and transmission fitness than the G1-B lineage strain <i>in vivo</i>, <i>ex vivo</i> and <i>in vitro</i>. Although based on prototype viruses, the results suggest that reassortment involving G57 genotype genes could enhance viral fitness and increase animal and human infection risk.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Copper(II) benzyloxychalcone analogues as new potential metallodrugs against SARS-CoV-2 replication.","authors":"Igor Andrade Santos, Victoria Riquena Grosche, Laiane Dos Santos Oliveira, Pedro Henrique de Souza Guarda, Gustavo Clauss Rodrigues, Rayany Cristina de Souza, Deborah Cristina Teixeira Alves, Andres Merits, Robinson Sabino-Silva, Dalan Bailey, Camilla Abbehausen, Mark Harris, Ana Carolina Gomes Jardim","doi":"10.1099/jgv.0.002245","DOIUrl":"https://doi.org/10.1099/jgv.0.002245","url":null,"abstract":"<p><p>Chalcones, a naturally occurring class of molecules found in various plants, serve as both precursors and final products in the biosynthesis of flavonoids. Renowned for their diverse therapeutic actions, chalcones demonstrate anti-inflammatory, antitumoral, antimalarial and antiviral activities. The structure of chalcones allows chemical manipulation, making them attractive for metal coordination, such as with copper, an essential metal for living organisms. Here, we characterize the activity of CuL₂phen and CuL₁phen against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in which L1 and L2 are two forms of the chalcones 3-(4-(benzyloxy)phenyl)-1-(4-fluoro-2-hydroxyphenyl)prop-2-en-1-one and 3-(4-(benzyloxy)phenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one, respectively, and phen is phenanthroline. CuL₁phen and CuL₂phen anti-SARS-CoV-2 activity were studied in the viral replication cycle employing both the SARS-CoV-2-NeonGreen infectious clone and wild-type isolates. The SI of CuL₁phen and CuL₂phen was found to be 1.7 and 5.5, respectively, demonstrating that CuL₂phen is a more promising compound. CuL₂phen impaired SARS-CoV-2 entry, predicted by molecular docking calculations to disrupt the glycoprotein S and angiotensin-converting enzyme 2 (ACE2) binding, emphasized by the low EC₅₀ in pseudotyped virus entry assay. Further, CuL₂phen was identified as SARS-CoV-2 post-entry inhibitor, probably due to its strong interaction with SARS-CoV-2 double stranded RNA. Altogether, the data suggest that CuL₂phen acts by impairing SARS-CoV-2 entry by disrupting the viral envelope as well as interrupting RNA replication through specifically intercalating into the dsRNA. The obtained results give us mechanistic insights into the activity of this promising Cu(II) metallodrug candidate in SARS-CoV-2 infection.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 4","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13141362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838817","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":"Stability of influenza viruses in the milk of cows and sheep.","authors":"Jenna Schafers, Caroline J Warren, Jiayun Yang, Junsen Zhang, Sarah J Cole, Jayne Cooper, Karolina Drewek, Natalie McGinn, Mehnaz Qureshi, Scott M Reid, Nunticha Pankaew, Wenfang Spring Tan, Sarah K Walsh, Ashley C Banyard, Ian Brown, Paul Digard, Munir Iqbal, Joe James, Thomas P Peacock, Edward Hutchinson","doi":"10.1099/jgv.0.002257","DOIUrl":"10.1099/jgv.0.002257","url":null,"abstract":"<p><p>In late 2023, H5N1 high-pathogenicity avian influenza virus (HPAIV) started circulating in dairy cattle in the USA. High viral titres were detected in milk from infected cows, raising concerns about onward human infections. Although pasteurisation was shown to effectively inactivate influenza viruses in milk, unpasteurised milk still poses a risk of infection, both from occupational exposure in dairies and from the consumption of raw milk. We therefore assessed how long influenza viruses could remain infectious in milk without heat inactivation. We examined the stability of a panel of influenza viruses in milk, including a contemporary H5N1 HPAIV and a variety of other influenza A and D viruses. We incubated viruses in cows' milk under laboratory conditions: at room temperature to simulate exposure in dairies and at 4 °C to simulate exposure to refrigerated raw milk. Following an isolated report of H5N1 viral RNA detection in milk from a sheep in the UK, we also carried out similar experiments with a laboratory strain of influenza A virus in sheep's milk. Although the survival of influenza viruses in milk was variable, we consistently found that, under laboratory conditions, substantial viral infectivity remained over periods when people might reasonably be exposed to infected milk - for over a day at room temperature and for more than 7 days when refrigerated. Our results highlight the zoonotic risk of H5N1 HPAIV in raw milk from infected animals and reinforce the importance of taking measures to mitigate this risk.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13151985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838876","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":"The MNV-1 protease-polymerase precursor cleaves a novel site in the NS1-2 protein.","authors":"Vernon K Ward, Geena M McKenzie-Goldsmith, Matt J Edwards, Vivienne L Young, Torsten Kleffmann, Louise A Stubbing, Andrew Siow, Margaret A Brimble","doi":"10.1099/jgv.0.002263","DOIUrl":"10.1099/jgv.0.002263","url":null,"abstract":"<p><p>Human noroviruses (HuNVs) are members of the <i>Caliciviridae</i> family and are a significant cause of gastroenteritis worldwide. Cell culture models are challenging for studying the intracellular replication of HuNV, with murine norovirus (MNV) routinely used to study norovirus replication. Norovirus genomes contain a non-structural (NS) polyprotein that is processed by the viral protease, generating precursor and mature proteins during replication. We identified a putative viral protease cleavage site at E⁶⁶/G⁶⁷ in the MNV-1 NS1-2 protein by sequence analysis that was cleaved by the protease-polymerase (ProPol) precursor but not Pro <i>in vitro</i> and during MNV-1 replication, with the cleavage site confirmed by MS. The P4-P4' LHAE⁶⁶/G⁶⁷PLA cleavage site of MNV-1 is conserved in some MNV strains, while other strains contain a predicted caspase cleavage site (LHAD⁶⁶/G⁶⁷PHA) at this position, indicating that cleavage of NS1 is widely conserved in MNV. Mutation of the ProPol cleavage site in MNV-1 NS1-2 to the caspase motif reduced viral protein expression and replication in Huh7CD300lf and BV2 cells, while removal of the site via an E⁶⁶A mutation caused a 100-fold reduction in viral yield in the naturally permissive BV-2 cell line. This study demonstrates that the protease function of the MNV-1 ProPol precursor has an important role during replication that is distinct to the mature protease and that cleavage of NS1-2 by ProPol at E⁶⁶/G⁶⁷ is important for MNV-1 replication.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 4","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147773376","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":"Synergistic antiviral effect of host Adipose Triglyceride Lipase-directed DABPU-DE with coronavirus RNA-dependent RNA polymerase-targeting remdesivir on feline infectious peritonitis virus.","authors":"Shaimaa Aboelmagd, Seok In Han, Ragab Farouk, Dae-Eun Cheong, Hae-Rang Seo, Dong Ju Lee, Sunwoo Lee, Kyoung-Oh Cho","doi":"10.1099/jgv.0.002261","DOIUrl":"https://doi.org/10.1099/jgv.0.002261","url":null,"abstract":"<p><p>Feline infectious peritonitis virus (FIPV) poses a significant threat to cats worldwide. Besides the limited development of antiviral drugs that mainly target virus proteins, concerns about resistance to mutant strains - similar to those seen in human and other mammalian viruses - remain high. Therefore, addressing these challenges involves developing innovative antiviral therapies, such as host-directed treatments that target host cell processes essential for viral replication. FIPV infection induced distinctive dynamics of lipid droplet (LD) remodelling, characterized by an increase in LD abundance from early to mid-infection, followed by a subsequent decline. Phosphorylated hormone-sensitive lipase, a key mediator of LD hydrolysis and fatty-acid release, became activated after the mid-infection phase, potentially contributing to elevated intracellular fatty-acid availability during late infection. Notably, atglistatin (DABPU-DM) and its derivatives robustly suppressed FIPV replication in Crandell-Rees feline kidney (CRFK) and feline macrophage Fcwf-4 cells, coincident with preservation of LD integrity and inhibition of LD breakdown. Among these compounds, DABPU-DE had the best selectivity index (686.0±35.2) against FIPV, with a higher half-maximal cytotoxic concentration (274.4±3.6 µM) and a lower half-maximal inhibitory concentration (0.4±0.02 µM). Moreover, combining DABPU-DE (0.18 µM) with remdesivir (1.35 µM), a viral RNA-dependent RNA polymerase inhibitor, showed a very strong synergistic effect (CI=0.09 and Bliss synergy score=14.46±1.80) in inhibiting FIPV replication in CRFK cells, even at lower doses than either drug alone. In conclusion, DABPU-DE is a promising antiviral candidate for FIPV, and its synergistic effect with remdesivir warrants further research in cats infected with FIPV.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 4","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147773442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ICTV Virus Taxonomy Profile: <i>Krittikaviridae</i> 2026.","authors":"Apoorva Prabhu, Christian Rinke","doi":"10.1099/jgv.0.002239","DOIUrl":"10.1099/jgv.0.002239","url":null,"abstract":"<p><p>The family <i>Krittikaviridae</i> includes dsDNA viruses associated with the marine archaeal lineage <i>Poseidoniales</i>. These viruses have been identified through metagenomic analysis of brackish estuarine samples and are closely related to other 'magroviruses'. The family belongs to the order <i>Magrovirales</i> and includes the genus <i>Velanvirus</i> and the species <i>Velanvirus brisbanense</i>. Viruses in the family have a genome of about 80 kbp that includes modules for DNA replication and virion morphogenesis. Krittikavirids are predicted to form virions with an icosahedral capsid and helical tail, characteristic of viruses belonging to the class <i>Caudoviricetes</i>. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family <i>Krittikaviridae</i>, which is available at ictv.global/report/krittikaviridae.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 4","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147638907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-release of tick-borne encephalitis virus RNA and structural proteins via virus-like particles and extracellular vesicles.","authors":"Ivana Křížová, Anna Klimešová, Alžběta Dostálková, Jana Racková, Jiřina Kaufmanová, Radim Novotný, Matěj Danda, Ivana Matošević, Zdeněk Franta, Hana Tykalová, Libor Grubhoffer, Michaela Rumlová","doi":"10.1099/jgv.0.002258","DOIUrl":"10.1099/jgv.0.002258","url":null,"abstract":"<p><p>Tick-borne encephalitis virus (TBEV) is a medically important flavivirus that causes severe neurological diseases in humans. The assembly of flaviviruses is initiated by the interaction between capsid (C) proteins and viral genomic RNA, yet the molecular determinants that govern RNA encapsidation remain unclear. In this study, we established a TBEV virus-like particle (VLP) system to analyse viral factors that influence viral RNA incorporation independently of productive infection. Using a reporter-containing TBEV minigenome, we investigated the contribution of UTRs to the incorporation of RNA into extracellular particles. Truncation of the 5' UTR, 3' UTR or both did not significantly affect the levels of minigenome RNA detected in pelleted extracellular fractions, indicating that RNA incorporation occurs largely in a non-specific manner. We further examined the role of C protein dimerization by introducing alanine substitutions into residues that form the α2-α2' and α4-α4' dimer interfaces. Paradoxically, these substitutions increased the levels of minigenome RNA detected in pelleted extracellular particles without altering intracellular RNA expression, indicating a complex relationship between the integrity of the C protein dimer interface and levels of extracellular viral RNA. Finally, we showed that TBEV proteins and minigenome RNA can be detected in extracellular vesicle (EV)-associated fractions under VLP-producing conditions. Using immunoaffinity purification, we demonstrate the presence of viral components in EVs, underscoring EV-associated release as a factor that complicates the analysis of flaviviral particle assembly.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 4","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147773446","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":"Broadly neutralizing monoclonal antibodies derived from mRNA LNP immunization exhibit potent neutralizing ability against JN.1, KP.3.1.1 and XEC new Omicron variants.","authors":"Hsiao-Ling Chiang, Hsiu-Ting Lin, Wan-Yu Chen, Kang-Hao Liang, Ruei-Min Lu, Han-Chung Wu","doi":"10.1099/jgv.0.002251","DOIUrl":"10.1099/jgv.0.002251","url":null,"abstract":"<p><p>Since the emergence of severe acute respiratory syndrome coronavirus 2 Omicron, dramatic changes in the receptor-binding domain have allowed for virus escape from many therapeutic antibodies. Development of antibodies effective against current viral strains is, therefore, necessary to provide useful clinical treatments and can also yield fundamental information about viral neutralization. Here, we utilized single B-cell antibody technology to isolate and characterize neutralizing antibodies from splenocytes of mice immunized with mRNA-LNPs. With this approach, we identified five BA.5 and four XBB.1.5 neutralizing chimeric antibodies (ChAbs). The identified ChAbs, BA.5-ChAb-41, XBB.1.5-ChAb-17 and XBB.1.5-ChAb-26, each potently neutralized BA.5, XBB.1.5 and JN.1 pseudotype viruses with low IC₅₀ (1.9, 2.3 and 10.93 ng ml^-1). Furthermore, XBB.1.5-ChAb-26 showed neutralizing capability against the current JN.1-related variants, KP.3.1.1 and XEC. By performing single amino acid substitution of the receptor-binding motif (RBM), we observed that the epitopes of BA.5-ChAb-41 and XBB.1.5-ChAb-17 include Y453 and R498 in the RBM. Moreover, XBB.1.5-ChAb-26 epitope includes Y453 and T500, which may contribute to its ability to neutralize JN.1, KP.3.1.1 and XEC variants. In summary, our approach allowed us to efficiently screen for highly functional antibodies, and we further identified critical residues in the epitopes to aid in the design of therapeutic virus-neutralizing antibodies.</p>","PeriodicalId":15880,"journal":{"name":"Journal of General Virology","volume":"107 4","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13131021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147773361","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}