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J Virol, April 1998, p. 2935-2944, Vol. 72, No. 4
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Functional Analysis of the Human Immunodeficiency Virus Type 1 Rev Protein Oligomerization Interface

Sarah L. Thomas,¹ Martin Oft,² Herbert Jaksche,¹ Georg Casari,³ Peter Heger,⁴ Marika Dobrovnik,¹ Dorian Bevec,¹ and Joachim Hauber^1,*

Department of Immunology, Novartis Research Institute, A-1235 Vienna,¹ and Research Institute of Molecular Pathology, A-1030 Vienna,² Austria, and Department of Biocomputing, EMBL, D-69117 Heidelberg,³ and Institute for Clinical and Molecular Virology, University of Erlangen-Nürnberg, D-91054 Erlangen,⁴ Germany

Received 16 June 1997/Accepted 22 December 1997

The expression of human immunodeficiency virus type 1 (HIV-1) structural proteins requires the action of the viral trans-regulatory protein Rev. Rev is a nuclear shuttle protein that directly binds to its cis-acting Rev response element (RRE) RNA target sequence. Subsequent oligomerization of Rev monomers on the RRE and interaction of Rev with a cellular cofactor(s) result in the cytoplasmic accumulation of RRE-containing viral mRNAs. Moreover, Rev by itself is exported from the nucleus to the cytoplasm. Although it has been demonstrated that Rev multimerization is critically required for Rev activity and hence for HIV-1 replication, the number of Rev monomers required to form a trans-activation-competent complex on the RRE is unknown. Here we report a systematic analysis of the putative multimerization domains within the Rev trans-activator protein. We identify the amino acid residues which are part of the proposed single hydrophobic surface patch in the Rev amino terminus that mediates intermolecular interactions. Furthermore, we show that the expression of a multimerization-deficient Rev mutant blocks HIV-1 replication in a trans-dominant (dominant-negative) fashion.

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^* Corresponding author. Present address: Institute for Clinical and Molecular Virology, University of Erlangen-Nürnberg, Schlossgarten 4, D-91054 Erlangen, Germany. Phone: 49-9131-85 6182. Fax: 49-9131-85 2101. E-mail: jmhauber{at}viro.med.uni-erlangen.de

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