rev and vif: their roles in hiv replication.

NLM AIDSLINE Rev and Vif: their roles in HIV replication. Simon JH; Meyer BE; Meinkoth JL; Fouchier RA; Malim MH; Howard Hughes
November 30, 1996

3rd Conf Retro and Opportun Infect. 1996 Jan 28-Feb 1;:178. Unique One of the striking differences between HIV and the type-B and -C oncogenic retroviruses is its possession of six genes in addition to gag, pol, and env. Accumulating evidence suggests that all six of these genes are required for efficient virus replication in vivo. As such, each may provide a novel target for future therapeutic strategies. An update or our efforts to understand the molecular basis for the function of two of these genes, rev and vif, will be presented. The rev protein is essential for the nucleocytoplasmic transport of all unspliced (intron containing) viral RNA. The protein itself has two discrete domains: an amino-terminal region confers binding to substrate RNA as well as nuclear localization whereas a carboxy-terminal region(the activation domain) mediates interactions with cellular cofactors and is required for Rev's own export out of the nucleus. We have recently demonstrated that the activation domain acts as a specific and autonomous nuclear export signal (NES), a finding that suggests that the critical targeting information that drives rev-RNA complexes into the cytoplasm resides within the Rev protein itself. Considerably less is currently known regarding vif. It has, however, been established that its presence in virus producing cells is required for the released virions to be infectious. Our results suggest that viruses expressed in the absence of vif are still able to penetrate target cells and initiate reverse transcription as efficiently as wild type virus. However, the reverse transcripts of vif-deficient virus infections fail to proceed to provirus formation and appear to be degraded by later timepoints. One explanation for this phenotype is that the viral pre-integration complexes disassemble inappropriately, this model might be consistent with the noted ultrastructural abnormalities of vif-deficient viruses. Genes, rev Genes, vif HIV/GENETICS/PHYSIOLOGY Transcription, Genetic Virus Replication/GENETICS ABSTRACT

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Information in this article was accurate in November 30, 1996. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.