JVI Figure table search 04
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sawaya, B. E.
Right arrow Articles by Amini, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sawaya, B. E.
Right arrow Articles by Amini, S.

 Previous Article  |  Next Article 

Journal of Virology, May 2000, p. 4877-4881, Vol. 74, No. 10
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Transdominant Activity of Human Immunodeficiency Virus Type 1 Vpr with a Mutation at Residue R73

Bassel E. Sawaya,1 Kamel Khalili,1 Jennifer Gordon,1 Alagarsamy Srinivasan,2 Max Richardson,1 Jay Rappaport,1 and Shohreh Amini1,*

Center for Neurovirology and Cancer Biology, Temple University, Philadelphia, Pennsylvania 19122,1 and Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, Pennsylvania 191072

Received 18 October 1999/Accepted 17 February 2000

The 96-amino-acid-long human immunodeficiency virus type 1 virion-encoded accessory protein Vpr is of particular interest, as this protein, which is found in association with viral particles, can exert a regulatory effect on both virus replication and host cell function. Evidently, Vpr, through interaction with several host regulatory proteins, can modulate transcription from the viral long terminal repeat promoter. Expression of Vpr in cells results in deregulation of cell proliferation during the cell cycle pathway at the G2 stage. Vpr has unique structural features consisting of multiple functional domains. In this study, we have focused on the leucine/isoleucine-rich domain near the carboxyl terminus of Vpr at residue 73 (arginine) and have demonstrated that alterations at this residue result in ablation of transcriptional activity of Vpr and its ability to block cell cycle events at the G2 stage. Interestingly, substitution mutations at R73 have resulted in a peptide with dominant negative activities on wild-type functions in transcription and host proliferation events. Results from in vitro and in vivo protein-protein interaction studies have revealed that functionally inactive mutant Vpr can be associated with wild-type protein, presumably through the N-terminal regions of the protein which have been shown to be important for Vpr oligomerization. Thus, it is likely that complexation of the mutant Vpr with wild-type protein functionally inactivates Vpr. The importance of these findings in light of the development of therapeutic strategies is discussed.

* Corresponding author. Mailing address: Center for Neurovirology and Cancer Biology, Temple University, 1900 N. 12th St., Philadelphia, PA 19122. Phone: (215) 204-0678. Fax: (215) 204-0679. E-mail: ashohreh{at}astro.temple.edu.

Journal of Virology, May 2000, p. 4877-4881, Vol. 74, No. 10
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. Mol. Cell. Biol. Microbiol. Mol. Biol. Rev.
Clin. Vaccine Immunol. ALL ASM JOURNALS

Copyright © 2000 by the American Society for Microbiology. All rights reserved.