Regulation of HIV‐1 gene expression

The quantity and quality of HIV‐1 gene expression is temporally controlled by a cascade of sequential regulatory interactions. Basal HIV‐1 transcription is determined by interaction of cellular regulatory proteins with specific DNA target sequences within the HIV‐1 long‐terminal repeat. The most notable of these protein: DNA interactions involves NF‐xB, a transcription factor that plays a pivotal role in the activation of genes important for cellular responses to infection and inflammation. A second level of control involves the virally encoded Tat trans‐activator. Tat, in combination with as yet unidentified cellular proteins, activates HIV‐1 gene expression through a specific interaction with the viral TAR RNA stem‐loop target sequence. A final level of regulation is mediated by the viral Rev protein. Rev acts posttranscriptionally to induce the expression of HIV‐1 structural proteins and thereby commits HIV‐1 to the late, cytopathic phase of the viral replication cycle. Rev activity appears to require a critical, threshold level of Rev protein expression, thus preventing entry into this late phase in cells that are unable to support efficient HIV‐1 gene expression. In total, this cascade of regulatory levels allows the HIV‐1 provirus to respond appropriately to the intracellular milieu present in each infected cell. In activated cells, the combination of Tat and Rev can stimulate a very high level of viral gene expression and replication. In quiescent or resting cells, in contrast, these same regulatory proteins are predicted to maintain the HIV‐1 provirus in a latent or nonproductive state.—Cullen, B. R. Regulation of HIV‐1 gene expression. FASEB J. 5: 2361–2368; 1991.

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