Abstract

RNAi plays important roles in many biological processes, including cellular defense against viral infection. Components of the RNAi machinery are widely conserved in plants and animals. In mammals, microRNAs (miRNAs) represent an abundant class of cell encoded small noncoding RNAs that participate in RNAi-mediated gene silencing. Here, findings that HIV-1 replication in cells can be regulated by miRNAs and that HIV-1 infection of cells can alter cellular miRNA expression are reviewed. Lessons learned from and questions outstanding about the complex interactions between HIV-1 and cellular miRNAs are discussed.

Highlights

  • RNAi is a biological mechanism widely conserved from yeast through humans (1)

  • RNases that participate in the generation of these small ncRNAs include: Drosha, Dicer, and Argonaute (Fig. 1). miRNA and siRNA biogenesis has been well described (2, 3), whereas Piwi-interacting RNA (piRNA) biogenesis is less well understood and in part involves the processing of single-stranded RNAs by yet identified ribonuclease(s) (9)

  • These investigators confirmed later that one of the five identified miRNAs inhibited nef expression, leading to repressed HIV replication in Jurkat cells (32). This effect was observed by Rana and colleagues (33), who predicted target sites for 11 miRNAs in the HIV-1 3Ј-UTR and further experimentally validated an inhibitory effect of miR-29a on HIV replication

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Summary

Introduction

RNAi is a biological mechanism widely conserved from yeast through humans (1). A key component of the RNAi machinery is the RNA-induced silencing complex (RISC),2 which, in its minimal form, is composed of an Argonaute protein and a small noncoding RNA (ncRNA) of ϳ22–30 nucleotides in length. Recent findings illustrate that many human miRNAs can target HIV-1 sequences and that HIV-1 infection can change the miRNA expression profiles in the circulating blood cells from infected individuals (25).

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