{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T21:31:20Z","timestamp":1789594280895,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013175","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000}}],"reference-count":64,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:00:00Z","timestamp":1758844800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01-AI134630"],"award-info":[{"award-number":["R01-AI134630"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"publisher","award":["P51-OD011092"],"award-info":[{"award-number":["P51-OD011092"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Liver dysfunction is more common and more severe among people with HIV than in the general population. Our previous transcriptomic analysis identified an increased hepatic type-1 interferon (IFN-1) response in simian immunodeficiency virus (SIV) infected rhesus macaques, including pronounced upregulation of the IFN-1 stimulated gene product MX1. Here, we interrogated the role of different cell types in the IFN-1 response, focusing on macrophage subsets. During the acute phase of SIV infection, the expression of MX1 in liver biopsies was elevated in the resident macrophage Kupffer cells (KCs, CD163\u2009+\u2009CD206+) as well as liver sinusoidal endothelial cells (LSECs, CD163\u2013 CD206+). Chronic infection was associated with increased MX1 expression both within KCs and the recruited monocyte-derived macrophages (MdMs, CD163\u2009+\u2009CD206\u2013) although the KCs were associated with the highest MX1 expression levels. We explored factors in the liver potentially associated with the macrophage IFN-1 response: 1) SIV DNA load, 2) bacterial DNA load (assessed via SIV DNA and 16S bacterial DNA qPCR, respectively), and 3) acute-phase hepatocyte lipid accumulation (steatosis). Both SIV and bacteria were elevated during chronic infection and directly correlated with MdM frequency. KC frequency did not correlate with SIV load but inversely correlated with bacterial load and also correlated directly with hepatocyte microvesicular steatosis in acute infection. Hepatocytes expressed variable levels of MX1 during acute and chronic infection. Overall, our data identify MdMs, LSECs and KCs as contributors to the heightened expression of MX1 in the liver during SIV infection. KCs express the highest levels of MX1 and therefore represent a potential target to reduce liver inflammation in people with HIV.<\/jats:p>","DOI":"10.1371\/journal.ppat.1013175","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T17:49:27Z","timestamp":1758908967000},"page":"e1013175","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Liver biopsies obtained throughout SIV infection reveal evolving interferon stimulated protein expression within distinct monocyte\/macrophage subsets"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3281-4880","authenticated-orcid":true,"given":"Nina","family":"Derby","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brooke 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M.","family":"Abraham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Savannah S.","family":"Lutz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cole","family":"Fisher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cristina","family":"Pacheco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy V.","family":"Smedley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin J.","family":"Burwitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald L.","family":"Sodora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,9,26]]},"reference":[{"issue":"10290","key":"ppat.1013175.ref001","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1016\/S0140-6736(20)32511-3","article-title":"Non-alcoholic fatty liver disease","volume":"397","author":"EE Powell","year":"2021","journal-title":"Lancet"},{"issue":"1","key":"ppat.1013175.ref002","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes","volume":"64","author":"ZM Younossi","year":"2016","journal-title":"Hepatology"},{"issue":"3","key":"ppat.1013175.ref003","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1038\/s41575-018-0082-x","article-title":"The role of macrophages in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis","volume":"16","author":"K Kazankov","year":"2019","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"7","key":"ppat.1013175.ref004","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/s41577-021-00639-3","article-title":"Immune cell-mediated features of non-alcoholic steatohepatitis","volume":"22","author":"T Huby","year":"2022","journal-title":"Nat Rev Immunol"},{"issue":"1","key":"ppat.1013175.ref005","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41575-018-0085-7","article-title":"HIV and the liver","volume":"16","author":"N Chamroonkul","year":"2019","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"1","key":"ppat.1013175.ref006","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s15010-010-0079-z","article-title":"Causes of death and risk factors among HIV-infected persons in the HAART era: analysis of a large urban cohort","volume":"39","author":"S 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