{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T12:24:51Z","timestamp":1781785491466,"version":"3.54.5"},"reference-count":64,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T00:00:00Z","timestamp":1752624000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Defense Threat Reduction Agency (DTRA)","award":["CB11311"],"award-info":[{"award-number":["CB11311"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Machupo virus (MACV), a member of the Arenaviridae family and causative agent of Bolivian hemorrhagic fever, results in lethality rates of 25\u201335% in humans. Mice lacking the signal transducer and activator of transcription 1 (STAT-1\u2212\/\u2212) have previously been shown to succumb to MACV infection within 7\u20138 days via the intraperitoneal route. Despite these reports, we observed partial lethality in STAT-1\u2212\/\u2212 mice following challenge with wild-type MACV. Serial sampling studies to evaluate the temporal progression of infection and pathologic changes after challenge revealed a two-phase disease course. The first phase was characterized by viral load and pathological lesions in the spleen, liver, and kidney followed by a second, lethal phase, defined by high viral titers and inflammation in the brain and spinal cord resulting in neurological manifestations and subsequent mortality. Tissue adaptation in the brains of challenged STAT-1\u2212\/\u2212 mice resulted in a fully lethal model in STAT-1\u2212\/\u2212 mice (mouse-adapted; maMACV). A similar two-phase disease course was observed following maMACV challenge, but more rapid dissemination of the virus to the brain and overall pathology in this region was observed. The outcome of these studies is a lethal small rodent model of MACV that recapitulates many aspects of human disease.<\/jats:p>","DOI":"10.3390\/v17070996","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T14:13:43Z","timestamp":1752761623000},"page":"996","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Characterization of a STAT-1 Knockout Mouse Model for Machupo Virus Infection and Pathogenesis"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5031-2534","authenticated-orcid":false,"given":"Stephanie R.","family":"Monticelli","sequence":"first","affiliation":[{"name":"Viral Immunology Branch, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA"},{"name":"The Geneva Foundation, Tacoma, WA 20817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana I.","family":"Kuehne","sequence":"additional","affiliation":[{"name":"The Geneva Foundation, Tacoma, WA 20817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell R.","family":"Bakken","sequence":"additional","affiliation":[{"name":"The Geneva Foundation, Tacoma, WA 20817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan R.","family":"Coyne","sequence":"additional","affiliation":[{"name":"Developmental Diagnostics Branch, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2231-5563","authenticated-orcid":false,"given":"Kenise D.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Chenega Corporation, Anchorage, AK 99503, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2669-9062","authenticated-orcid":false,"given":"Jo Lynne W.","family":"Raymond","sequence":"additional","affiliation":[{"name":"Pathology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3526-8755","authenticated-orcid":false,"given":"Xiankun","family":"Zeng","sequence":"additional","affiliation":[{"name":"Pathology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua B.","family":"Richardson","sequence":"additional","affiliation":[{"name":"Cherokee Nation Integrated Health, Catoosa, OK 74015, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1401-8670","authenticated-orcid":false,"given":"Zebulon","family":"Lapoint","sequence":"additional","affiliation":[{"name":"Cherokee Nation Integrated Health, Catoosa, OK 74015, USA"},{"name":"Center for Genome Science, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Williams","sequence":"additional","affiliation":[{"name":"Cherokee Nation Integrated Health, Catoosa, OK 74015, USA"},{"name":"Center for Genome Science, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4891-447X","authenticated-orcid":false,"given":"Christopher P.","family":"Stefan","sequence":"additional","affiliation":[{"name":"Developmental Diagnostics Branch, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey R.","family":"Kugelman","sequence":"additional","affiliation":[{"name":"Center for Genome Science, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey W.","family":"Koehler","sequence":"additional","affiliation":[{"name":"Operational Diagnostics Branch, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5256-7733","authenticated-orcid":false,"given":"Andrew S.","family":"Herbert","sequence":"additional","affiliation":[{"name":"The Geneva Foundation, Tacoma, WA 20817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"103","DOI":"10.4269\/ajtmh.1966.15.103","article-title":"Isolation of Machupo virus from wild rodent Calomys callosus","volume":"15","author":"Johnson","year":"1966","journal-title":"Am. 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