trans-Dominant inhibition of human immunodeficiency virus type 1 Rev occurs through formation of inactive protein complexes

Thomas J. Hope, Nicola P. Klein, Melissa E. Elder, Tristram G. Parslow*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

Abstract

The human immunodeficiency virus type 1 Rev protein controls expression of certain viral RNAs by binding to these RNAs in the nucleus. To investigate how dominant negative Rev mutants inhibit Rev function, we fused such mutants to hormone-dependent localization signals from the glucocorticoid receptor. Each was found to have fully potent inhibitory activity whether expressed in the nucleus or in the cytoplasm. Wild-type Rev colocalized with an inhibitory fusion protein, implying that the two proteins interact. The resulting complexes accumulated within nuclei in response to steroids but had no effect on expression of Rev-responsive mRNAs. A mutation known to block in vitro oligomerization of Rev abolished both complex formation and inhibitory activity of the mutant fusion proteins. Thus, trans-dominant inhibition of Rev does not require competition for nuclear substrates but may instead reflect the ability of a mutant to form nonfunctional complexes with the wild-type protein in vivo.

Original languageEnglish (US)
Pages (from-to)1849-1855
Number of pages7
JournalJournal of virology
Volume66
Issue number4
DOIs
StatePublished - 1992

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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