{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T20:30:05Z","timestamp":1785529805877,"version":"3.56.0"},"reference-count":87,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T00:00:00Z","timestamp":1670889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute (NCI)","doi-asserted-by":"publisher","award":["R01 CA239263"],"award-info":[{"award-number":["R01 CA239263"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute (NCI)","doi-asserted-by":"publisher","award":["#1830867"],"award-info":[{"award-number":["#1830867"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Science Foundation Award","award":["R01 CA239263"],"award-info":[{"award-number":["R01 CA239263"]}]},{"name":"National Science Foundation Award","award":["#1830867"],"award-info":[{"award-number":["#1830867"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Epidemic Kaposi\u2019s sarcoma (KS), defined by co-infection with Human Herpes Virus 8 (HHV-8) and the Human Immunodeficiency Virus (HIV), is a major cause of mortality in sub-Saharan Africa. Antiretroviral therapy (ART) significantly reduces the risk of developing KS, and for those with KS, tumors frequently resolve with ART alone. However, for unknown reasons, a significant number of KS cases do not resolve and can progress to death. To explore how HIV responds to ART in the KS tumor microenvironment, we sequenced HIV env-nef found in DNA and RNA isolated from plasma, peripheral blood mononuclear cells, and tumor biopsies, before and after ART, in four Ugandan study participants who had unresponsive or progressive KS after 180\u2013250 days of ART. We performed immunohistochemistry experiments to detect viral proteins in matched formalin-fixed tumor biopsies. Our sequencing results showed that HIV diversity and RNA expression in KS tumors are maintained after ART, despite undetectable plasma viral loads. The presence of spliced HIV transcripts in KS tumors after ART was consistent with a transcriptionally active viral reservoir. Immunohistochemistry staining found colocalization of HIV Nef protein and tissue-resident macrophages in the KS tumors. Overall, our results demonstrated that even after ART reduced plasma HIV viral load to undetectable levels and restored immune function, HIV in KS tumors continues to be transcriptionally and translationally active, which could influence tumor maintenance and progression.<\/jats:p>","DOI":"10.3390\/v14122774","type":"journal-article","created":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T04:32:48Z","timestamp":1670905968000},"page":"2774","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The Persistence of HIV Diversity, Transcription, and Nef Protein in Kaposi\u2019s Sarcoma Tumors during Antiretroviral Therapy"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9114-7002","authenticated-orcid":false,"given":"David J.","family":"Nolan","sequence":"first","affiliation":[{"name":"Bioinfoexperts, LLC, Thibodaux, LA 70301, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Rose","sequence":"additional","affiliation":[{"name":"Bioinfoexperts, LLC, Thibodaux, LA 70301, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongzhen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Departments of Laboratory Medicine, Pathology and Medicine, The University of California at San Francisco, San Francisco, CA 94110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Leong","sequence":"additional","affiliation":[{"name":"Departments of Laboratory Medicine, Pathology and Medicine, The University of California at San Francisco, San Francisco, CA 94110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary B.","family":"Fogel","sequence":"additional","affiliation":[{"name":"Natural Selection, Inc., San Diego, CA 92127, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa L. S.","family":"Scholte","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Tropical Medicine, The George Washington University, Washington, DC 20037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey M.","family":"Bethony","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Tropical Medicine, The George Washington University, Washington, DC 20037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paige","family":"Bracci","sequence":"additional","affiliation":[{"name":"The AIDS and Cancer Specimen Resource, San Francisco, CA 94110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna L.","family":"Lamers","sequence":"additional","affiliation":[{"name":"Bioinfoexperts, LLC, Thibodaux, LA 70301, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7232-2602","authenticated-orcid":false,"given":"Michael S.","family":"McGrath","sequence":"additional","affiliation":[{"name":"Departments of Laboratory Medicine, Pathology and Medicine, The University of California at San Francisco, San Francisco, CA 94110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1126\/science.7997879","article-title":"Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi\u2019s sarcoma","volume":"266","author":"Chang","year":"1994","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1007\/s40257-017-0270-4","article-title":"Diagnosis and Treatment of Kaposi Sarcoma","volume":"18","author":"Schneider","year":"2017","journal-title":"Am. 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