Subtype C HIV-1 reservoirs throughout the body in ART-suppressed individuals

• Published in: JCI insight Vol. 7; no. 20
• Main Authors: Liu, Zhou, Julius, Peter, Kang, Guobin, West, John T, Wood, Charles
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 24.10.2022; American Society for Clinical investigation
• Subjects: AIDS/HIV; Formaldehyde; HIV Infections - drug therapy; HIV-1 - genetics; Humans; Proviruses - genetics; RNA; Virology; AIDS/HIV; AIDS vaccine; Molecular biology; Virology
• ISSN: 2379-3708; 2379-3708
• DOI: 10.1172/jci.insight.162604

Subtype B HIV-1 reservoirs have been intensively investigated, but reservoirs in other subtypes and how they respond to antiretroviral therapy (ART) is substantially less established. To characterize subtype C HIV-1 reservoirs, we implemented postmortem frozen, as well as formalin fixed paraffin embedded (FFPE) tissue sampling of central nervous system (CNS) and peripheral tissues. HIV-1 LTR, gag, envelope (env) DNA and RNA was quantified using genomic DNA and RNA extracted from frozen tissues. RNAscope was used to localize subtype C HIV-1 DNA and RNA in FFPE tissue. Despite uniform viral load suppression in our cohort, PCR results showed that subtype C HIV-1 proviral copies vary both in magnitude and tissue distribution, with detection primarily in secondary lymphoid tissues. Interestingly, the appendix harbored proviruses in all subjects. Unlike subtype B, subtype C provirus was rarely detectable in the CNS, and there was no detectable HIV-1 RNA. HIV-1 RNA was detected in peripheral lymphoid tissues of 6 out of 8 ART-suppressed cases. In addition to active HIV-1 expression in lymphoid tissues, RNAscope revealed HIV RNA detection in CD4-expressing cells in the appendix, suggesting that this tissue was a previously unreported potential treatment-resistant reservoir for subtype C HIV-1.