Suppression of MicroRNA-Silencing Pathway by HIV-1 During Virus Replication

TLDR

MicroRNAs are short noncoding RNAs that regulate gene expression and serve as a host defense against viruses. The study demonstrates that the miRNA‑silencing machinery physiologically controls HIV‑1 replication. Dicer and Drosha inhibit HIV‑1 replication in infected and latently infected cells, while HIV‑1 suppresses the miR‑17/92 cluster—a suppression required for efficient replication and dependent on Tat cofactor PCAF—underscoring the miRNA‑silencing pathway’s role in HIV‑1 replication and latency.

Abstract

MicroRNAs (miRNAs) are single-stranded noncoding RNAs of 19 to 25 nucleotides that function as gene regulators and as a host cell defense against both RNA and DNA viruses. We provide evidence for a physiological role of the miRNA-silencing machinery in controlling HIV-1 replication. Type III RNAses Dicer and Drosha, responsible for miRNA processing, inhibited virus replication both in peripheral blood mononuclear cells from HIV-1–infected donors and in latently infected cells. In turn, HIV-1 actively suppressed the expression of the polycistronic miRNA cluster miR-17/92. This suppression was found to be required for efficient viral replication and was dependent on the histone acetyltransferase Tat cofactor PCAF. Our results highlight the involvement of the miRNA-silencing pathway in HIV-1 replication and latency.