HIV-1 structural gene expression requires the binding of multiple Rev monomers to the viral RRE: implications for HIV-1 latency.
Expression of the structural proteins of HIV-1 requires the direct interaction of the viral Rev trans-activator with its cis-acting RNA target sequence, the Rev response element or RRE. Here, we demonstrate that this specific RNA-binding event is, as expected, mediated by the conserved arginine-rich motif of Rev. However, we also show that amino acid residues located proximal to this basic domain that are critical for in vivo Rev function are dispensable for sequence-specific binding to the RRE. Instead, these sequences are required for the multimerization of Rev on the viral RRE target sequence. The observation that Rev function requires the sequential binding of multiple Rev molecules to the RRE provides a biochemical explanation for the observed threshold effect for Rev function in vivo and suggests a molecular model for the high incidence of latent infection by HIV-1.
Malim
M H
MH
Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710.
Cullen
B R
BR
D003001:Cloning, Molecular; D004926:Escherichia coli / Q000235:genetics; D015967:Gene Expression Regulation, Viral; D015694:Gene Products, rev / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D005814:Genes, Viral; D015757:Genes, rev; D005822:Genetic Vectors; D005982:Glutathione Transferase / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D046911:Macromolecular Substances; D016296:Mutagenesis; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification / Q000378:metabolism; D014158:Transcription, Genetic; D015678:Viral Structural Proteins / Q000235:genetics*; D014779:Virus Replication; D054321:rev Gene Products, Human Immunodeficiency Virus
D015694:Gene Products, rev; D046911:Macromolecular Substances; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D015678:Viral Structural Proteins; D054321:rev Gene Products, Human Immunodeficiency Virus; D005982:Glutathione Transferase