Functional dissection of the HIV-1 Rev trans-activator--derivation of a trans-dominant repressor of Rev function.

Journal Article

Human immunodeficiency virus type 1 (HIV-1) encodes a nuclear trans-activator, termed Rev, that is required for the expression of the viral structural proteins and, hence, for viral replication. The Rev protein acts posttranscriptionally to induce the sequence-specific nuclear export of unspliced HIV-1 mRNA species that are otherwise excluded from the cell cytoplasm. We have used site-directed mutagenesis to identify two distinct regions of the HIV-1 Rev protein that are required for in vivo biological activity. The larger and more N-terminal of these two regions includes, but extends beyond, an arginine-rich sequence element required for nuclear localization. Mutation of a second, more C-terminal Rev protein sequence element was found to yield defective Rev proteins that act as trans-dominant inhibitors of Rev function. These Rev mutants are shown to inhibit HIV-1 replication when expressed in transfected cells and may have potential application in the treatment of HIV-1 related disease.

Full Text

Duke Authors

Cited Authors

  • Malim, MH; Böhnlein, S; Hauber, J; Cullen, BR

Published Date

  • July 14, 1989

Published In

Volume / Issue

  • 58 / 1

Start / End Page

  • 205 - 214

PubMed ID

  • 2752419

International Standard Serial Number (ISSN)

  • 0092-8674

Language

  • eng

Conference Location

  • United States