Evaluating lncRNA Expression Patterns during HIV-1 Treatment Interruption

Int J Mol Sci. 2023 Jan 5;24(2):1031. doi: 10.3390/ijms24021031.

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.

Keywords: GAS5; HEAL; HIV-1; MALAT1; NEAT1; NRON; biomarker; lncRNA; treatment interruption.

MeSH terms

  • Anti-Retroviral Agents / therapeutic use
  • HIV Infections* / drug therapy
  • HIV Infections* / genetics
  • HIV-1*
  • Humans
  • Leukocytes, Mononuclear
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / therapeutic use
  • Viral Load

Substances

  • RNA, Long Noncoding
  • Anti-Retroviral Agents