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Journal of Virology, August 2002, p. 8079-8089, Vol. 76, No. 16
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.16.8079-8089.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

The Carboxy-Terminal Region of the Human Immunodeficiency Virus Type 1 Protein Rev Has Multiple Roles in Mediating CRM1-Related Rev Functions

Yoshiyuki Hakata,1,2 Masami Yamada,1 Naoto Mabuchi,1 and Hisatoshi Shida1*

Institute for Genetic Medicine, Hokkaido University, Hokkaido 060-0815,1 Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan2

Received 20 November 2001/ Accepted 12 May 2002

The human immunodeficiency virus type 1 (HIV-1) regulatory protein, Rev, mediates the nuclear export of unspliced and singly spliced viral mRNAs by bridging viral RNA and export receptor human CRM1 (hCRM1). Ribonucleoprotein complex formation, including the oligomerization of Rev proteins on viral RNA, must occur to allow export. We show here that Rev-Rev interactions, which are a basis of complex formation, can be initiated without cellular factors and are subsequently enhanced by hCRM1-Ran-GTP. Furthermore, we reveal functions for the Rev carboxy-terminal (C-terminal) region, which is well conserved among many HIV-1 strains, and for which no function has been reported. This region is required for the efficient binding of Rev to hCRM1 and consequently for nuclear export, Rev-Rev dimerization, and full Rev transactivator activity. Consistent with these results, a HIV-1 proviral plasmid that expresses a C-terminally truncated Rev mutant protein produces smaller amounts of the p24 antigen than does a plasmid that possesses an intact rev gene. These results indicate the functional importance of the C-terminal region for full Rev activity, which leads to efficient HIV-1 replication.

* Corresponding author. Mailing address: Institute for Genetic Medicine, Hokkaido University, Hokkaido 060-0815, Japan. Phone and fax: 81-11-707-6837. E-mail: hshida{at}imm.hokudai.ac.jp.

Journal of Virology, August 2002, p. 8079-8089, Vol. 76, No. 16
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.16.8079-8089.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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