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-kappa B, 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
BR
Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710.
D001354:Avian Leukosis Virus / Q000235:genetics; D001426:Bacterial Proteins; D001483:Base Sequence; D002628:Chemoreceptor Cells; D029968:Escherichia coli Proteins; D015967:Gene Expression Regulation, Viral; D015693:Gene Products, nef / Q000502:physiology; D016346:Gene Products, vif / Q000502:physiology; D016336:Gene Products, vpr / Q000502:physiology; D015757:Genes, rev / Q000502:physiology; D015756:Genes, tat / Q000502:physiology; D016325:HIV Long Terminal Repeat / Q000235:genetics / Q000502:physiology; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D054298:Human Immunodeficiency Virus Proteins; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000502:physiology; D012313:RNA / Q000096:biosynthesis; D011956:Receptors, Cell Surface; D014158:Transcription, Genetic; D054334:Viral Regulatory and Accessory Proteins / Q000502:physiology; D054311:nef Gene Products, Human Immunodeficiency Virus; D054320:vif Gene Products, Human Immunodeficiency Virus; D054325:vpr Gene Products, Human Immunodeficiency Virus; D000086082:Viroporin Proteins
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D015693:Gene Products, nef; D016346:Gene Products, vif; D016336:Gene Products, vpr; D054298:Human Immunodeficiency Virus Proteins; D008565:Membrane Proteins; D016328:NF-kappa B; D012313:RNA; D011956:Receptors, Cell Surface; D054334:Viral Regulatory and Accessory Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus; D054320:vif Gene Products, Human Immunodeficiency Virus; D054325:vpr Gene Products, Human Immunodeficiency Virus; C057331:Tar protein, E coli; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins