HIV-1 transcription dominates over host gene activity at the HIV-1 integration site

ABSTRACT: HIV-1 persists as an integrated DNA provirus in infected cells. Antiretroviral therapy (ART) does not inhibit HIV-1 promoter activity. It is often assumed that HIV-1 reactivation versus latency passively follows host gene activation and repression near the HIV-1 integration site. HIV-1 proviruses integrated into active genes are then transcriptionally active, typically resulting in immune clearance of infected cells. HIV-1 proviruses integrated into repressive chromatin conversely escape immune surveillance. To understand how host gene activity affects HIV-1 transcription, we examined how CRISPR-mediated activation and inhibition of host genes affected HIV-1 nearby chromatin accessibility and RNA transcription using qPCR, ATAC-seq, and strand-specific RNA-seq, in seven Jurkat T cell clones having known HIV-1 integration site. We further examined host CRISPR-mediated HIV-1 activation and inhibition effects on host chromatin accessibility and RNA transcription. We found that host gene activation at the integration site decreased HIV-1 transcription, while host gene inhibition frequently increased HIV-1 transcription. Changes to transcription occurred in both HIV-1 orientations relative to the host gene. Particularly at same-orientation integration sites, reductions in HIV-1 transcription were accompanied by reduced chromatin accessibility at the HIV-1 promoter. However, when HIV-1 integrated in close proximity to host transcription start site, host gene activation increased HIV-1 transcription. When HIV-1 integrated into a non-genic region, we found that HIV-1 increased host chromatin accessibility, remained transcriptionally active, and drove high level of aberrant host RNA transcription. Overall, we found that instead of passively following host gene activity, HIV-1 shapes host chromatin accessibility while an interplay of host factors and transcriptional interference modulate its expression.

ORGANISM(S): Homo sapiens

PROVIDER: GSE302199 | GEO | 2025/10/21

REPOSITORIES: GEO