{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:42:03Z","timestamp":1791895323648,"version":"4.3.4"},"reference-count":25,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,17]],"date-time":"2023-03-17T00:00:00Z","timestamp":1679011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011094","name":"Public Health Agency of Canada","doi-asserted-by":"publisher","award":["A-base"],"award-info":[{"award-number":["A-base"]}],"id":[{"id":"10.13039\/100011094","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Nigeria experiences annual outbreaks of Lassa fever (LF) with high case numbers. At least three clades of Lassa virus (LASV) have been documented in Nigeria, though recent outbreaks are most often associated with clade II or clade III viruses. Using a recently isolated clade III LASV from a case of LF in Nigeria in 2018, we developed and characterized a guinea pig adapted virus capable of causing lethal disease in commercially available Hartley guinea pigs. Uniform lethality was observed after four passages of the virus and was associated with only two dominant genomic changes. The adapted virus was highly virulent with a median lethal dose of 10 median tissue culture infectious doses. Disease was characterized by several hallmarks of LF in similar models including high fever, thrombocytopenia, coagulation disorders, and increased inflammatory immune mediators. High viral loads were noted in all solid organ specimens analyzed. Histological abnormalities were most striking in the lungs and livers of terminal animals and included interstitial inflammation, edema, and steatosis. Overall, this model represents a convenient small animal model for a clade III Nigeria LASV with which evaluation of specific prophylactic vaccines and medical countermeasures can be conducted.<\/jats:p>","DOI":"10.3390\/v15030769","type":"journal-article","created":{"date-parts":[[2023,3,17]],"date-time":"2023-03-17T04:10:48Z","timestamp":1679026248000},"page":"769","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["An Outbred Guinea Pig Disease Model for Lassa Fever Using a Host-Adapted Clade III Nigerian Lassa Virus"],"prefix":"10.3390","volume":"15","author":[{"given":"Yvon","family":"Deschambault","sequence":"first","affiliation":[{"name":"Special Pathogens, National Microbiology Laboratory Branch, Public Health Agency of Canada, Winnipeg, MB R3E 3M4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoff","family":"Soule","sequence":"additional","affiliation":[{"name":"Special Pathogens, National Microbiology Laboratory Branch, Public Health Agency of Canada, Winnipeg, MB R3E 3M4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8535-0733","authenticated-orcid":false,"given":"Levi","family":"Klassen","sequence":"additional","affiliation":[{"name":"Special Pathogens, National Microbiology Laboratory Branch, Public Health Agency of Canada, Winnipeg, MB R3E 3M4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Sloan","sequence":"additional","affiliation":[{"name":"Special Pathogens, National Microbiology Laboratory Branch, Public Health Agency of Canada, Winnipeg, MB R3E 3M4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Audet","sequence":"additional","affiliation":[{"name":"Special Pathogens, National Microbiology Laboratory Branch, Public Health Agency of Canada, Winnipeg, MB R3E 3M4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Azaransky","sequence":"additional","affiliation":[{"name":"Special Pathogens, National Microbiology Laboratory Branch, Public Health Agency of Canada, Winnipeg, MB R3E 3M4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulmajid S.","family":"Musa","sequence":"additional","affiliation":[{"name":"Nigerian Centre for Disease Control, Jabi, Abuja 900108, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adama","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Nigerian Centre for Disease Control, Jabi, Abuja 900108, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afolabi M.","family":"Akinpelu","sequence":"additional","affiliation":[{"name":"Nigerian Centre for Disease Control, Jabi, Abuja 900108, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nwando","family":"Mba","sequence":"additional","affiliation":[{"name":"Nigerian Centre for Disease Control, Jabi, Abuja 900108, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek R.","family":"Stein","sequence":"additional","affiliation":[{"name":"Special Pathogens, National Microbiology Laboratory Branch, Public Health Agency of Canada, Winnipeg, MB R3E 3M4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Ranson","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Manitoba, Winnipeg, MB R3E 3P5, Canada"},{"name":"Shared Health Diagnostic Services, Winnipeg, MB R3C 3H8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhamad","family":"Almiski","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Manitoba, Winnipeg, MB R3E 3P5, Canada"},{"name":"Shared Health Diagnostic Services, Winnipeg, MB R3C 3H8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Tierney","sequence":"additional","affiliation":[{"name":"Special Pathogens, National Microbiology Laboratory Branch, Public Health Agency of Canada, Winnipeg, MB R3E 3M4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabor","family":"Fischer","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Manitoba, Winnipeg, MB R3E 3P5, Canada"},{"name":"Shared Health Diagnostic Services, Winnipeg, MB R3C 3H8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mable","family":"Chan","sequence":"additional","affiliation":[{"name":"Special Pathogens, National Microbiology Laboratory Branch, Public Health Agency of Canada, Winnipeg, MB R3E 3M4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Safronetz","sequence":"additional","affiliation":[{"name":"Special Pathogens, National Microbiology Laboratory Branch, Public Health Agency of Canada, Winnipeg, MB R3E 3M4, Canada"},{"name":"Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"670","DOI":"10.4269\/ajtmh.1970.19.670","article-title":"Lassa fever, a new virus disease of man from West Africa. I. Clinical description and pathological findings","volume":"19","author":"Frame","year":"1970","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_2","first-page":"1","article-title":"Lassa fever in West African sub-region: An overview","volume":"44","author":"Ogbu","year":"2007","journal-title":"J. Vector Borne Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1093\/infdis\/155.3.437","article-title":"A Prospective Study of the Epidemiology and Ecology of Lassa Fever","volume":"155","author":"McCormick","year":"1987","journal-title":"J. Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Bell-Kareem, A.R., and Smither, A.R. (2021). Epidemiology of Lassa Fever, Springer Nature.","DOI":"10.1007\/82_2021_234"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1126\/science.185.4147.263","article-title":"Lassa virus isolation from Mastomys natalensis rodents during an epidemic in Sierra Leone","volume":"185","author":"Monath","year":"1974","journal-title":"Science"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1111\/j.1863-2378.2012.01469.x","article-title":"Lassa Fever in West Africa: Evidence for an Expanded Region of Endemicity","volume":"59","author":"Sogoba","year":"2012","journal-title":"Zoonoses Public Health"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.coviro.2019.06.005","article-title":"A short history of Lassa fever: The first 10\u201315 years after discovery","volume":"37","author":"Monath","year":"2019","journal-title":"Curr. Opin. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1136\/bmj.311.7009.857","article-title":"Review of cases of nosocomial Lassa fever in Nigeria: The high price of poor medical practice","volume":"311","author":"Tomori","year":"1995","journal-title":"BMJ"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/S1473-3099(18)30121-X","article-title":"Clinical and laboratory predictors of Lassa fever outcome in a dedicated treatment facility in Nigeria: A retrospective, observational cohort study","volume":"18","author":"Okokhere","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"170","DOI":"10.3389\/fpubh.2019.00170","article-title":"Corrigendum: Caseload and Case Fatality of Lassa Fever in Nigeria, 2001\u20132018: A Specialist Center\u2019s Experience and Its Implications","volume":"7","author":"Akpede","year":"2019","journal-title":"Front. Public Health"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1093\/trstmh\/traa011","article-title":"Lassa fever in pregnancy: A systematic review and meta-analysis","volume":"114","author":"Kayem","year":"2020","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.3201\/eid2506.181035","article-title":"Epidemiologic and clinical features of lassa fever outbreak in Nigeria, January 1\u2013May 6, 2018","volume":"25","author":"Ilori","year":"2019","journal-title":"Emerg. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Chika-Igwenyi, N.M., Harrison, R.E., Psarra, C., Gil-Cuesta, J., Gulamhusein, M., Onwe, E.O., Onoh, R.C., Unigwe, U.S., Ajayi, N.A., and Nnadozie, U.U. (2021). Early onset of neurological features differentiates two outbreaks of lassa fever in Ebonyi state, Nigeria during 2017\u20132018. PLoS Negl. Trop. Dis., 15.","DOI":"10.1371\/journal.pntd.0009169"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"76","DOI":"10.11604\/pamj.2019.34.76.16425","article-title":"Lassa virus RNA detection from suspected cases in Nigeria, 2011\u20132017","volume":"34","author":"Babalola","year":"2019","journal-title":"Pan Afr. Med. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/s40249-018-0421-8","article-title":"Re-emerging Lassa fever outbreaks in Nigeria: Re-enforcing \u2018One Health\u2019 community surveillance and emergency response practice","volume":"7","author":"Tambo","year":"2018","journal-title":"Infect. Dis. Poverty"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.3201\/eid2808.211787","article-title":"Lack of Evidence for Ribavirin Treatment of Lassa Fever in Systematic Review of Published and Unpublished Studies","volume":"28","author":"Cheng","year":"2022","journal-title":"Emerg. Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"vii","DOI":"10.1016\/j.coviro.2019.09.001","article-title":"Editorial overview: Lassa virus","volume":"37","author":"Schmaljohn","year":"2019","journal-title":"Curr. Opin. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Sattler, R.A., Paessler, S., Ly, H., and Huang, C. (2020). Animal models of lassa fever. Pathogens, 9.","DOI":"10.3390\/pathogens9030197"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"14775","DOI":"10.1038\/srep14775","article-title":"The broad-spectrum antiviral favipiravir protects Guinea pigs from lethal Lassa virus infection post-disease onset","volume":"5","author":"Safronetz","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Stein, D.R., Warner, B.M., Audet, J., Soule, G., Siragam, V., Sroga, P., Griffin, B.D., Leung, A., Grolla, A., and Tierney, K. (2021). Differential pathogenesis of closely related 2018 Nigerian outbreak clade III Lassa virus isolates. PLoS Pathog., 17.","DOI":"10.1371\/journal.ppat.1009966"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1093\/infdis\/jit004","article-title":"A recently isolated Lassa virus from Mali demonstrates atypical clinical disease manifestations and decreased virulence in cynomolgus macaques","volume":"207","author":"Safronetz","year":"2013","journal-title":"J. Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.antiviral.2007.10.002","article-title":"Animal models of highly pathogenic RNA viral infections: Hemorrhagic fever viruses","volume":"78","author":"Gowen","year":"2008","journal-title":"Antivir. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.antiviral.2014.10.001","article-title":"Animal models of viral hemorrhagic fever","volume":"112","author":"Smith","year":"2014","journal-title":"Antivir. Res."},{"key":"ref_24","unstructured":"Safronetz, D., Feldmann, H., and Falzarano, D. (2012). Medical Microbiology, Churchill Livingstone. [18th ed.]."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Safronetz, D., Mire, C., Rosenke, K., Feldmann, F., Haddock, E., Geisbert, T., and Feldmann, H. (2015). A Recombinant Vesicular Stomatitis Virus-Based Lassa Fever Vaccine Protects Guinea Pigs and Macaques against Challenge with Geographically and Genetically Distinct Lassa Viruses. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0003736"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/3\/769\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:57:16Z","timestamp":1760122636000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/3\/769"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,17]]},"references-count":25,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["v15030769"],"URL":"https:\/\/doi.org\/10.3390\/v15030769","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,17]]}}}