In vivo detection of antisense HIV-1 transcripts in untreated and ART-treated individuals

Area of Science:

• Virology
• Molecular Biology
• Immunology

Background:

• Natural antisense transcripts (AST) are known to regulate gene expression in various organisms.
• In vitro studies suggest HIV-1 AST can induce viral latency via epigenetic silencing of the 5' long terminal repeat.
• In vivo evidence for HIV-1 AST expression has been lacking.

Purpose of the Study:

• To demonstrate the in vivo expression of natural antisense transcripts (AST) in HIV-1.
• To investigate the presence of HIV-1 AST in unstimulated peripheral blood mononuclear cells (PBMCs) from people with HIV-1 (PWH).
• To explore the potential role of AST in HIV-1 persistence, particularly during antiretroviral therapy (ART).

Main Methods:

• Employed single RNA template amplification and sequencing.
• Analyzed unstimulated PBMCs from people with HIV-1 (PWH).
• Compared AST expression levels in individuals on ART versus untreated individuals.

Main Results:

• Successfully demonstrated in vivo expression of HIV-1 AST in unstimulated PBMCs from PWH.
• Observed potentially higher AST expression levels in individuals undergoing ART compared to untreated individuals.
• Confirmed that persistent infected cell clones under ART continue to express HIV AST.

Conclusions:

• This study provides the first direct, sequence-verified evidence of HIV-1 AST expression in vivo, occurring naturally without cellular activation.
• Findings suggest AST may be naturally present in PWH and could contribute to HIV-1 persistence.
• Further research into targeting AST in viral reservoirs may offer novel strategies for HIV remission without ART.