Evaluating lncRNA Expression Patterns during HIV-1 Treatment Interruption

Abstract

Lately, the interest in long non-coding RNAs (lncRNAs) as potential drug targets and predictive markers in the context of HIV-1 has peaked, but their in vivo expression and regulation remains largely unexplored. Therefore, the present study examined lncRNA expression patterns during a clinical antiretroviral treatment interruption (ATI) trial. Peripheral blood mononuclear cells were isolated from ten patients at four timepoints: prior to ATI, 7–15 days after stop, at viral rebound and 3 months post antiretroviral therapy re-initiation. RNA was extracted and RT-qPCR on five known HIV-1-related lncRNAs (HEAL, MALAT1, NEAT1, GAS5 and NRON) was performed and correlated with HIV-1 and host marker expression. All lncRNAs correlated stronger with interferon stimulated genes (ISGs) than with HIV-1 reservoir and replication markers. However, one lncRNA, HEAL, showed significant upregulation at viral rebound during ATI compared to baseline and re-initiation of therapy (p = 0.0010 and p = 0.0094, respectively), following a similar viral-load-driven expression pattern to ISGs. In vitro knockdown of HEAL caused a significant reduction in HIV-1 infection levels, validating HEAL’s importance for HIV-1 replication. We conclude that the HIV-1-promoting lncRNA HEAL is upregulated at viral rebound during ATI, most likely induced by viral cues.

Identification of a circulating long non-coding RNA signature panel in plasma as a novel biomarker for the detection of acute/early-stage HIV-1 infection

“…Several lncRNAs in this study displayed pronounced aberrant expression patterns during HIV-1 infection, and these lncRNAs returned to normal expression levels following ART. Consistent with our findings in the present investigation, Zhaou et al found a restoration in the level of lncRNAs with therapy [ 49 , 50 ].…”

“…On the other hand, circulating lncRNAs that are detectable by qPCR and originate from cell-derived microvesicles, exosomes, apoptotic vesicle bodies, and other undiscovered routes may be used as possible indicators of HIV-1 infection. Circulating lncRNAs have been discovered in a few studies that may act as biomarkers for HIV-1 infection [ 23 , 49 , 50 ]. None of the earlier reports have evaluated the ability of circulating lncRNAs to detect both the eclipse stage and the acute/early stage of HIV-1 infection.…”