{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T19:04:47Z","timestamp":1789499087268,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.ppat.1014511","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000}}],"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["390873048"],"award-info":[{"award-number":["390873048"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["369799452"],"award-info":[{"award-number":["369799452"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014895","name":"Open Philanthropy Project","doi-asserted-by":"publisher","award":["GV673603826"],"award-info":[{"award-number":["GV673603826"]}],"id":[{"id":"10.13039\/100014895","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Institute for Human Infections and Immunity"},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["K99AI156012"],"award-info":[{"award-number":["K99AI156012"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R00AI156012"],"award-info":[{"award-number":["R00AI156012"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Crimean-Congo hemorrhagic fever (CCHF), which is caused by infection with the CCHF virus (CCHFV), is the most widespread hemorrhagic infectious disease. In severe cases, liver damage is a salient manifestation. However, the detailed mechanism is not yet fully understood. To investigate the pathogenesis of CCHF-related liver damage, we infected type I interferon receptor 1 knockout (IFNAR1\n                    <jats:sup>-\/-<\/jats:sup>\n                    ) mice with Hazara virus (HAZV), which is a surrogate pathogen of CCHFV, as well as with the CCHFV itself. HAZV infection caused CCHF-like symptoms, including severe liver damage, alongside inflammatory responses. HAZV infection in IFNAR1\n                    <jats:sup>-\/-<\/jats:sup>\n                    mice additionally lacking mitochondrial antiviral signaling protein (MAVS) induced minimal cytokine responses; however, these mice still exhibited weight loss and liver damage, albeit with a significantly delayed onset of lethal outcomes. We found that loss of liver-resident macrophage, Kupffer cells, occurred prior to viral spread in hepatocytes and liver damage in these mice. Notably, mice lacking IFNAR1 in Kupffer cells, but not mice lacking IFNAR1 in hepatocytes, also lost Kupffer cell population and exhibited lethal liver damage, following HAZV and CCHFV infection. Our findings indicate that IFNAR1 signaling in mononuclear phagocytes, especially Kupffer cells, is essential for preventing viral spread and fatal liver damage and raise the possibility that inflammatory cytokines- and viral replication-mediated Kupffer cell loss synergistically drives both processes.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014511","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T17:40:27Z","timestamp":1787074827000},"page":"e1014511","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Loss of type I interferon signaling in Kupffer cells triggers viral spread and fatal liver damage in a mouse model of Crimean-Congo hemorrhagic fever"],"prefix":"10.1371","volume":"22","author":[{"given":"Shintaro","family":"Yamada","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Shimojima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junki","family":"Maruyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9571-4895","authenticated-orcid":true,"given":"Hiroki","family":"Kato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"issue":"5","key":"ppat.1014511.ref001","first-page":"847","article-title":"Crimean Congo hemorrhagic fever virus for clinicians-virology, 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