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

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

T J Hope et al. J Virol. 1992 Apr.

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.

Similar articles

• Nuclear export of the human immunodeficiency virus type 1 nucleocytoplasmic shuttle protein Rev is mediated by its activation domain and is blocked by transdominant negative mutants.

  Szilvay AM, Brokstad KA, Kopperud R, Haukenes G, Kalland KH. Szilvay AM, et al. J Virol. 1995 Jun;69(6):3315-23. doi: 10.1128/JVI.69.6.3315-3323.1995. J Virol. 1995. PMID: 7745679 Free PMC article.

• Analysis of intracellular trafficking and interactions of cytoplasmic HIV-1 Rev mutants in living cells.

  Stauber RH, Afonina E, Gulnik S, Erickson J, Pavlakis GN. Stauber RH, et al. Virology. 1998 Nov 10;251(1):38-48. doi: 10.1006/viro.1998.9295. Virology. 1998. PMID: 9813201

• Inhibition of human immunodeficiency virus type 1 Rev function by a Rev mutant which interferes with nuclear/nucleolar localization of Rev.

  Kubota S, Furuta R, Maki M, Hatanaka M. Kubota S, et al. J Virol. 1992 Apr;66(4):2510-3. doi: 10.1128/JVI.66.4.2510-2513.1992. J Virol. 1992. PMID: 1548775 Free PMC article.

Cited by

• Engineering human immunodeficiency virus 1 protease heterodimers as macromolecular inhibitors of viral maturation.

  McPhee F, Good AC, Kuntz ID, Craik CS. McPhee F, et al. Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11477-81. doi: 10.1073/pnas.93.21.11477. Proc Natl Acad Sci U S A. 1996. PMID: 8876160 Free PMC article.

• Human chromosome 6- and 11-encoded factors support human immunodeficiency virus type 1 Rev function in A9 cells.

  Shukla RR, Marques SM, Kimmel PL, Kumar A. Shukla RR, et al. J Virol. 1996 Dec;70(12):9064-8. doi: 10.1128/JVI.70.12.9064-9068.1996. J Virol. 1996. PMID: 8971045 Free PMC article.

• Involvement of human CRM1 (exportin 1) in the export and multimerization of the Rex protein of human T-cell leukemia virus type 1.

  Hakata Y, Umemoto T, Matsushita S, Shida H. Hakata Y, et al. J Virol. 1998 Aug;72(8):6602-7. doi: 10.1128/JVI.72.8.6602-6607.1998. J Virol. 1998. PMID: 9658105 Free PMC article.

• Polyvalent Rev decoys act as artificial Rev-responsive elements.

  Symensma TL, Baskerville S, Yan A, Ellington AD. Symensma TL, et al. J Virol. 1999 May;73(5):4341-9. doi: 10.1128/JVI.73.5.4341-4349.1999. J Virol. 1999. PMID: 10196332 Free PMC article.

• Mutational analysis of bovine leukemia virus Rex: identification of a dominant-negative inhibitor.

  Choi EA, Hope TJ. Choi EA, et al. J Virol. 2005 Jun;79(11):7172-81. doi: 10.1128/JVI.79.11.7172-7181.2005. J Virol. 2005. PMID: 15890956 Free PMC article.

References

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Atypon
  • Europe PubMed Central
  • PubMed Central

• Other Literature Sources

  • The Lens - Patent Citations Database