The Persistence of HIV Diversity, Transcription, and Nef Protein in Kaposi’s Sarcoma Tumors during Antiretroviral Therapy

Autor: David J. Nolan, Rebecca Rose, Rongzhen Zhang, Alan Leong, Gary B. Fogel, Larissa L. S. Scholte, Jeffrey M. Bethony, Paige Bracci, Susanna L. Lamers, Michael S. McGrath
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Viruses, Vol 14, Iss 12, p 2774 (2022)
Druh dokumentu: article
ISSN: 14122774
1999-4915
30453798
DOI: 10.3390/v14122774
Popis: Epidemic Kaposi’s 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 180–250 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.
Databáze: Directory of Open Access Journals
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