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Subtype C HIV-1 reservoirs throughout the body in ART-suppressed individuals
Zhou Liu, … , John T. West, Charles Wood
Zhou Liu, … , John T. West, Charles Wood
Published October 24, 2022
Citation Information: JCI Insight. 2022;7(20):e162604. https://doi.org/10.1172/jci.insight.162604.
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Research Article AIDS/HIV Virology

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

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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.

Authors

Zhou Liu, Peter Julius, Guobin Kang, John T. West, Charles Wood

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Figure 2

Subtype C HIV-1 DNA in aviremic brain tissues.

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Subtype C HIV-1 DNA in aviremic brain tissues.
(A) Heatmap of subtype C ...
(A) Heatmap of subtype C HIV-1 DNA in aviremic brain tissues. A heatmap displaying the abundance of 3 subtype C HIV-1 DNA (LTR, gag, and env) in different brain regions of 8 aviremic subjects was generated by qPCR analysis. Blocks with colors indicate undetectable (0) DNA copy (blue) to increase DNA copies (brown, up to 93 copies/1 × 106 cells). CNS tissues from the same hemisphere were analyzed (left). (B) Copy numbers of subtype C HIV-1 DNA detected in aviremic brain. The different regions harboring viral DNA and the viral DNA copy numbers in the brain of the 8 aviremic subjects were shown. There was no detectable viral DNA in the parietal lobe, temporal lobe, and cerebellum of 8 aviremic cases. HIV-1 DNA copies were identified by qPCR with 100 ng genomic DNA as a template. HIV-1 LTR (blue), gag (green), and env (red) DNA copy numbers were calculated as the mean of triplicate qPCR reactions and normalized to 1 million cells. The rectangles mark 3 tissues that have all 3 viral genes, indicating potential intact viral genome in those tissues.

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