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 Dautin, N.
Right arrow Articles by Ladant, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dautin, N.
Right arrow Articles by Ladant, D.

 Previous Article  |  Next Article 

Journal of Virology, August 2003, p. 8216-8226, Vol. 77, No. 15
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.15.8216-8226.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Human Immunodeficiency Virus (HIV) Type 1 Transframe Protein Can Restore Activity to a Dimerization-Deficient HIV Protease Variant

Nathalie Dautin,* Gouzel Karimova, and Daniel Ladant

Unité de Biochimie des Interactions Macromoléculaires, Département de Biologie Structurale et Chimie, CNRS URA 2185, Institut Pasteur, 75724 Paris Cedex 15, France

Received 4 February 2003/ Accepted 3 May 2003

The protease (PR) from human immunodeficiency virus (HIV) is essential for viral replication: this aspartyl protease, active only as a dimer, is responsible for cleavage of the viral polyprotein precursors (Gag and Gag-Pol), to release the functional mature proteins. In this work, we have studied the structure-function relationships of the HIV PR by combining a genetic test to detect proteolytic activity in Escherichia coli and a bacterial two-hybrid assay to analyze PR dimerization. We showed that a drug-resistant PR variant isolated from a patient receiving highly active antiretroviral therapy is impaired in its dimerization capability and, as a consequence, is proteolytically inactive. We further showed that the polypeptide regions adjacent to the PR coding sequence in the Gag-Pol polyprotein precursor, and in particular, the transframe polypeptide (TF), located at the N terminus of PR, can facilitate the dimerization of this variant PR and restore its enzymatic activity. We propose that the TF protein could help to compensate for folding and/or dimerization defects in PR arising from certain mutations within the PR coding sequence and might therefore function to buffer genetic variations in PR.

* Corresponding author. Mailing address: Unité de Biochimie des Interactions Macromoléculaires, Département de Biologie Structurale et Chimie, Institut Pasteur, 28, rue du Docteur Roux, 75724 Paris Cedex 15, France. Phone: 33 (1) 45 68 83 88. Fax: 33 (1) 40 61 30 43. E-mail: ndautin{at}pasteur.fr.

Journal of Virology, August 2003, p. 8216-8226, Vol. 77, No. 15
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.15.8216-8226.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Leiherer, A., Ludwig, C., Wagner, R. (2009). Uncoupling Human Immunodeficiency Virus Type 1 gag and pol Reading Frames: Role of the Transframe Protein p6* in Viral Replication. J. Virol. 83: 7210-7220 [Abstract] [Full Text]  
  • Chatterjee, A., Mridula, P., Mishra, R. K., Mittal, R., Hosur, R. V. (2005). Folding Regulates Autoprocessing of HIV-1 Protease Precursor. J. Biol. Chem. 280: 11369-11378 [Abstract] [Full Text]  
  • Pettit, S. C., Everitt, L. E., Choudhury, S., Dunn, B. M., Kaplan, A. H. (2004). Initial Cleavage of the Human Immunodeficiency Virus Type 1 GagPol Precursor by Its Activated Protease Occurs by an Intramolecular Mechanism. J. Virol. 78: 8477-8485 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»