RNA interference and HIV-1: hits and misses

Abstract

PURPOSE OF REVIEW: RNA interference is a type of nucleic-acid-based immunity used by cells to restrict transposons, transgenes and viruses. The RNA interference machinery targets long double-stranded RNAs to produce short RNAs that arm cellular ribonucleases to degrade foreign RNAs in a sequence-specific manner. Despite this defense, many viruses with RNA genomes, such as HIV-1, replicate seemingly unrestricted in cells. This suggests that viruses may have evolved counter-strategems that negate the host's RNA interference. We review the complex point-counterpoint RNA interference interplays between the human cells and HIV-1. RECENT FINDINGS: RNA interference functions in human cells to restrict viral replication. Recent findings suggest that HIV-1 can evade cellular RNA interference in several ways. First, the virus can mutate its sequence to evade sequence-specific targeting by RNA interference. Second, HIV-1 encodes a viral Tat protein that can partially suppress the cell's RNA interference processing machinery. Finally, HIV-1 encodes a small RNA decoy, TAR, which can sequester a cellular protein named TAR RNA binding protein. The recent discovery that TAR RNA binding protein is a required cofactor for Dicer to process microRNA and small interfering RNA suggests that TAR RNA is another moiety used by HIV-1 to defeat RNA interference. SUMMARY: We discuss stratagems used by HIV-1 and other viruses to defeat the cells' antiviral small interfering RNA/microRNA defenses. We review how viruses might control and regulate host genes by encoding viral microRNA.