Regulation of expression of human immunodeficiency virus

Abstract

Human immunodeficiency virus (HIV), the causative agent of acquired immune deficiency syndrome (AIDS), encodes regulatory factors necessary for its expression. The study of these factors clearly indicates the importance and complexity of post-trascriptional processes in regulating gene expression. Two regulatory proteins, Tat and Rev, are necessary for viral replication. These small nuclear proteins accumulate primarily in the nucleoli and act on HIV via sequence-specific elements found on the viral RNA. Both the Tat responsive element (TAR) and the Rev responsive element (RRE) map within regions of strong RNA secondary structure. While all viral mRNAs contain TAR, only the mRNAs producing HIV structural proteins contain RRE. Tat increases the levels of all viral mRNAs. Its function is complex and involves transcriptional and possibly post-transcriptional steps. Rev promotes the transport of viral mRNAs containing RRE from the nucleus to the cytoplasm and increases the half-life of these viral mRNAs. A third factor, Nef, is a cytoplasmic myristylated protein that has been proposed to down-regulate virus expression. These factors are integrated in a feedback regulatory network that dictates the balanced expression of viral components. The study of HIV expression in human cells will advance our understanding of the mechanisms related to the pathogenicity of HIV. This knowledge may also lead to novel diagnostic and therapeutic approaches to combat AIDS.