{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T21:39:36Z","timestamp":1789421976867,"version":"build-2803163510"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,6,21]],"date-time":"2025-06-21T00:00:00Z","timestamp":1750464000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K99AI156012"],"award-info":[{"award-number":["K99AI156012"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R00AI156012"],"award-info":[{"award-number":["R00AI156012"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01AI151801"],"award-info":[{"award-number":["U01AI151801"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Institute for Human Infections and Immunity"},{"DOI":"10.13039\/100006988","name":"John S Dunn Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006988","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Lassa virus (LASV) is the causative agent of Lassa fever (LF), a severe hemorrhagic disease with potential for lethal outcomes. Classified as a risk group 4 pathogen, it represents a significant public health threat in endemic regions. Our laboratory previously developed a novel lethal guinea pig model of Lassa fever using the clinical isolate LASV strain LF2384. However, the specific pathogenic factors underlying LF2384 infection in guinea pigs remained unclear. In this study, we aimed to investigate the immunological differences elicited by LF2384 and LF2350, another LASV strain isolated from a nonlethal case within the same outbreak. We compared the expression kinetics of key immune-related genes in guinea pigs infected with either LF2384 or LF2350. Using reverse genetics, we identified the L protein as a critical viral factor responsible for the observed pathogenic differences between the strains.<\/jats:p>","DOI":"10.1093\/infdis\/jiaf323","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T07:48:19Z","timestamp":1749714499000},"page":"e839-e848","source":"Crossref","is-referenced-by-count":5,"title":["Identification of Factors Contributing to Pathogenic Variability Among Lassa Virus Strains Using the Guinea Pig Model and Reverse Genetics"],"prefix":"10.1093","volume":"232","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2066-1979","authenticated-orcid":false,"given":"Satoshi","family":"Taniguchi","sequence":"first","affiliation":[{"name":"Department of Pathology, The University of Texas Medical Branch , Galveston, Texas ,","place":["USA"]},{"name":"Department of Virology I, National Institute of Infectious Diseases , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Pathology, The University of Texas Medical Branch , Galveston, Texas ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruchi","family":"Paroha","sequence":"additional","affiliation":[{"name":"Department of Pathology, The University of Texas Medical Branch , Galveston, Texas ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pathology, The University of Texas Medical Branch , Galveston, Texas ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Slobodan","family":"Paessler","sequence":"additional","affiliation":[{"name":"Department of Pathology, The University of Texas Medical Branch , Galveston, Texas ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0088-4793","authenticated-orcid":false,"given":"Junki","family":"Maruyama","sequence":"additional","affiliation":[{"name":"Department of Pathology, The University of Texas Medical Branch , Galveston, Texas ,","place":["USA"]},{"name":"Institute for Human Infections and Immunity, The University of Texas Medical Branch , Galveston, Texas ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,6,21]]},"reference":[{"key":"2025112208030331800_jiaf323-B1","first-page":"52","article-title":"High Lassa fever activity in northern part of Edo State, Nigeria: reanalysis of confirmatory test results","volume":"17","author":"Eze","year":"2013","journal-title":"Afr J Health Sci"},{"key":"2025112208030331800_jiaf323-B2","doi-asserted-by":"crossref","first-page":"232","DOI":"10.3389\/fpubh.2018.00232","article-title":"Lassa fever 2016 outbreak in Plateau State, Nigeria\u2014the changing epidemiology and clinical presentation","volume":"6","author":"Shehu","year":"2018","journal-title":"Front Public Heal"},{"key":"2025112208030331800_jiaf323-B3","doi-asserted-by":"crossref","first-page":"262","DOI":"10.2105\/AJPH.2017.304186","article-title":"Mortality among confirmed Lassa fever cases during the 2015\u20132016 outbreak in Nigeria","volume":"108","author":"Buba","year":"2018","journal-title":"Am J Public Health"},{"key":"2025112208030331800_jiaf323-B4","doi-asserted-by":"crossref","first-page":"e2748","DOI":"10.1371\/journal.pntd.0002748","article-title":"Lassa fever in post-conflict Sierra Leone","volume":"8","author":"Shaffer","year":"2014","journal-title":"PLoS Negl Trop Dis"},{"key":"2025112208030331800_jiaf323-B5","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1093\/trstmh\/trv047","article-title":"Mapping the zoonotic niche of Lassa fever in Africa","volume":"109","author":"Mylne","year":"2015","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"2025112208030331800_jiaf323-B6","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1586\/erv.12.139","article-title":"The search for animal models for Lassa fever vaccine development","volume":"12","author":"Lukashevich","year":"2013","journal-title":"Expert Rev Vaccines"},{"key":"2025112208030331800_jiaf323-B7","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1186\/1743-422X-8-205","article-title":"Pathogenesis of Lassa fever in cynomolgus macaques","volume":"8","author":"Hensley","year":"2011","journal-title":"Virol J"},{"key":"2025112208030331800_jiaf323-B8","doi-asserted-by":"crossref","first-page":"e00428-19","DOI":"10.1128\/mSphere.00428-19","article-title":"Lethal infection of Lassa virus isolated from a human clinical sample in outbred guinea pigs without adaptation","volume":"4","author":"Maruyama","year":"2019","journal-title":"MSphere"},{"key":"2025112208030331800_jiaf323-B9","doi-asserted-by":"crossref","first-page":"2920","DOI":"10.1128\/JVI.02948-15","article-title":"Animal model of sensorineural hearing loss associated with Lassa virus infection","volume":"90","author":"Yun","year":"2016","journal-title":"J Virol"},{"key":"2025112208030331800_jiaf323-B10","doi-asserted-by":"crossref","first-page":"e0008555","DOI":"10.1371\/journal.pntd.0008555","article-title":"A single mutation (V64G) within the RING domain of Z attenuates Junin virus","volume":"14","author":"Hallam","year":"2020","journal-title":"PLoS Negl Trop Dis"},{"key":"2025112208030331800_jiaf323-B11","doi-asserted-by":"crossref","first-page":"e114261","DOI":"10.1371\/journal.pone.0114261","article-title":"Use of a guinea pig-specific transcriptome array for evaluation of protective immunity against genital chlamydial infection following intranasal vaccination in guinea pigs","volume":"9","author":"Wali","year":"2014","journal-title":"PLoS One"},{"key":"2025112208030331800_jiaf323-B12","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1007\/s12033-014-9813-6","article-title":"Development and utilization of a custom PCR array workflow: analysis of gene expression in Mycoplasma genitalium and guinea pig (Cavia porcellus)","volume":"57","author":"Veselenak","year":"2015","journal-title":"Mol Biotechnol"},{"key":"2025112208030331800_jiaf323-B13","doi-asserted-by":"crossref","first-page":"e01964-23","DOI":"10.1128\/jvi.01964-23","article-title":"Development of reverse genetics system for Guanarito virus: substitution of E1497K in the L protein of Guanarito virus S-26764 strain changes plaque phenotype and growth kinetics","volume":"98","author":"Taniguchi","year":"2024","journal-title":"J Virol"},{"key":"2025112208030331800_jiaf323-B14","doi-asserted-by":"crossref","first-page":"4663","DOI":"10.1073\/pnas.0600652103","article-title":"Recovery of an arenavirus entirely from RNA polymerase I\/II-driven cDNA","volume":"103","author":"Flatz","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2025112208030331800_jiaf323-B15","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/0378-1119(91)90434-D","article-title":"Efficient selection for high-expression transfectants with a novel eukaryotic vector","volume":"108","author":"Hitoshi","year":"1991","journal-title":"Gene"},{"key":"2025112208030331800_jiaf323-B16","doi-asserted-by":"crossref","first-page":"896","DOI":"10.3390\/v12080896","article-title":"Analysis of the function of the lymphocytic choriomeningitis virus S segment untranslated region on growth capacity in vitro and on virulence in vivo","volume":"12","author":"Taniguchi","year":"2020","journal-title":"Viruses"},{"key":"2025112208030331800_jiaf323-B17","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1385\/IR:35:3:263","article-title":"The CD94\/NKG2 family of receptors: from molecules and cells to clinical relevance","volume":"35","author":"Borrego","year":"2006","journal-title":"Immunol Res"},{"key":"2025112208030331800_jiaf323-B18","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/j.immuni.2011.02.015","article-title":"CD94 is essential for NK cell-mediated resistance to a lethal viral disease","volume":"34","author":"Fang","year":"2011","journal-title":"Immunity"},{"key":"2025112208030331800_jiaf323-B19","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1002\/eji.201142099","article-title":"NK cells are strongly activated by Lassa and Mopeia virus-infected human macrophages in vitro but do not mediate virus suppression","volume":"42","author":"Russier","year":"2012","journal-title":"Eur J Immunol"},{"key":"2025112208030331800_jiaf323-B20","doi-asserted-by":"crossref","first-page":"2766","DOI":"10.3390\/v4112766","article-title":"Immune responses and Lassa virus infection","volume":"4","author":"Russier","year":"2012","journal-title":"Viruses"},{"key":"2025112208030331800_jiaf323-B21","doi-asserted-by":"crossref","first-page":"2186","DOI":"10.1128\/JVI.74.5.2186-2192.2000","article-title":"Characterization of human CD4+ T-cell clones recognizing conserved and variable epitopes of the Lassa virus nucleoprotein","volume":"74","author":"ter Meulen","year":"2000","journal-title":"J Virol"},{"key":"2025112208030331800_jiaf323-B22","doi-asserted-by":"crossref","first-page":"747324","DOI":"10.3389\/fimmu.2021.747324","article-title":"Interleukin-7 biology and its effects on immune cells: mediator of generation, differentiation, survival, and homeostasis","volume":"12","author":"Chen","year":"2021","journal-title":"Front Immunol"},{"key":"2025112208030331800_jiaf323-B23","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1038\/nri1708","article-title":"Regulation of MHC class II gene expression by the class II transactivator","volume":"5","author":"Reith","year":"2005","journal-title":"Nat Rev Immunol"},{"key":"2025112208030331800_jiaf323-B24","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/S1471-4906(01)02003-8","article-title":"The MHC class II transactivator: prey and hunter in infectious diseases","volume":"22","author":"Accolla","year":"2001","journal-title":"Trends Immunol"},{"key":"2025112208030331800_jiaf323-B25","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1126\/science.abb3753","article-title":"MHC class II transactivator CIITA induces cell resistance to Ebola virus and SARS-like coronaviruses","volume":"370","author":"Bruchez","year":"2020","journal-title":"Science"},{"key":"2025112208030331800_jiaf323-B26","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1186\/1471-2164-15-960","article-title":"Lassa and Marburg viruses elicit distinct host transcriptional responses early after infection","volume":"15","author":"Caballero","year":"2014","journal-title":"BMC Genomics"},{"key":"2025112208030331800_jiaf323-B27","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s42003-020-01543-7","article-title":"Systemic viral spreading and defective host responses are associated with fatal Lassa fever in macaques","volume":"4","author":"Baillet","year":"2021","journal-title":"Commun Biol"},{"key":"2025112208030331800_jiaf323-B28","doi-asserted-by":"crossref","first-page":"e1012768","DOI":"10.1371\/journal.ppat.1012768","article-title":"Fatal Lassa fever in cynomolgus monkeys is associated with systemic viral dissemination and inflammation","volume":"20","author":"Hortion","year":"2024","journal-title":"PLOS Pathog"},{"key":"2025112208030331800_jiaf323-B29","doi-asserted-by":"crossref","first-page":"6635","DOI":"10.1128\/JVI.00044-13","article-title":"Identification of virulence determinants within the L genomic segment of the Pichinde arenavirus","volume":"87","author":"McLay","year":"2013","journal-title":"J Virol"},{"key":"2025112208030331800_jiaf323-B30","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1023\/A:1008016724243","article-title":"Sequence comparison of the large genomic RNA segments of two strains of lymphocytic choriomeningitis virus differing in pathogenic potential for guinea pigs","volume":"17","author":"Djavani","year":"1998","journal-title":"Virus Genes"},{"key":"2025112208030331800_jiaf323-B31","doi-asserted-by":"crossref","first-page":"13934","DOI":"10.1128\/JVI.79.22.13934-13942.2005","article-title":"A live attenuated vaccine for Lassa fever made by reassortment of Lassa and Mopeia viruses","volume":"79","author":"Lukashevich","year":"2005","journal-title":"J Virol"},{"key":"2025112208030331800_jiaf323-B32","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1128\/jvi.55.3.704-709.1985","article-title":"Genetic mapping of lymphocytic choriomeningitis virus pathogenicity: virulence in guinea pigs is associated with the L RNA segment","volume":"55","author":"Riviere","year":"1985","journal-title":"J Virol"},{"key":"2025112208030331800_jiaf323-B33","doi-asserted-by":"crossref","first-page":"239","DOI":"10.3390\/v15010239","article-title":"Growth, pathogenesis, and serological characteristics of the Japanese encephalitis virus genotype IV recent strain 19CxBa-83-Cv","volume":"15","author":"Tajima","year":"2023","journal-title":"Viruses"},{"key":"2025112208030331800_jiaf323-B34","doi-asserted-by":"crossref","first-page":"e02882","DOI":"10.1016\/j.heliyon.2019.e02882","article-title":"E and prM proteins of genotype V Japanese encephalitis virus are required for its increased virulence in mice","volume":"5","author":"Tajima","year":"2019","journal-title":"Heliyon"},{"key":"2025112208030331800_jiaf323-B35","doi-asserted-by":"crossref","first-page":"769","DOI":"10.3390\/v15030769","article-title":"An outbred guinea pig disease model for Lassa fever using a host-adapted clade III Nigerian Lassa virus","volume":"15","author":"Deschambault","year":"2023","journal-title":"Viruses"},{"key":"2025112208030331800_jiaf323-B36","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1038\/s41564-021-00916-w","article-title":"Cryo-EM structures of Lassa and Machupo virus polymerases complexed with cognate regulatory Z proteins identify targets for antivirals","volume":"6","author":"Xu","year":"2021","journal-title":"Nat Microbiol"},{"key":"2025112208030331800_jiaf323-B37","doi-asserted-by":"crossref","first-page":"240","DOI":"10.3389\/fcimb.2018.00240","article-title":"The S genome segment is sufficient to maintain pathogenicity in intra-clade Lassa virus reassortants in a guinea pig model","volume":"8","author":"Welch","year":"2018","journal-title":"Front Cell Infect Microbiol"},{"key":"2025112208030331800_jiaf323-B38","doi-asserted-by":"crossref","first-page":"112654","DOI":"10.1016\/j.jim.2019.112654","article-title":"Development of an anti-guinea pig CD4 monoclonal antibody for depletion of CD4+ T cells in vivo","volume":"474","author":"Banasik","year":"2019","journal-title":"J Immunol Methods"}],"container-title":["The Journal of Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jid\/advance-article-pdf\/doi\/10.1093\/infdis\/jiaf323\/63538489\/jiaf323.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/232\/5\/e839\/63538489\/jiaf323.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/232\/5\/e839\/63538489\/jiaf323.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T13:03:16Z","timestamp":1763816596000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jid\/article\/232\/5\/e839\/8170146"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,21]]},"references-count":38,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,6,21]]},"published-print":{"date-parts":[[2025,11,14]]}},"URL":"https:\/\/doi.org\/10.1093\/infdis\/jiaf323","relation":{},"ISSN":["0022-1899","1537-6613"],"issn-type":[{"value":"0022-1899","type":"print"},{"value":"1537-6613","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,11,15]]},"published":{"date-parts":[[2025,6,21]]}}}