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

Authors

Zhou Liu, University of Nebraska-Lincoln, Louisiana State University Health Sciences CenterFollow
Peter Julius, University of Zambia
Guobin Kang, Louisiana State University Health Sciences Center
John T. West, Louisiana State University Health Sciences Center
Charles Wood, Louisiana State University Health Sciences Center

Date of this Version

10-24-2022

Citation

JCI Insight. 2022;7(20):e162604. https://doi.org/10.1172/jci. insight.162604.

Comments

Open access.

Abstract

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.