HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 31, 32426-32434, July 30, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/31/32426    most recent M313137200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hemonnot, B. Articles by Briant, L. Search for Related Content PubMed PubMed Citation Articles by Hemonnot, B. Articles by Briant, L. Social Bookmarking                      What's this?

The Host Cell MAP Kinase ERK-2 Regulates Viral Assembly and Release by Phosphorylating the p6^gag Protein of HIV-1^*

Bénédicte Hemonnot¶, Christine Cartier||, Bernard Gay, Sandra Rebuffat, Martine Bardy, Christian Devaux, Véronique Boyer**, and Laurence Briant

From the Laboratoire Infections Rétrovirales et Signalisation Cellulaire, Centre National pour la Recherche Scientifique, UMR 5121-Université Montpellier 1, Institut de Biologie, 4 Boulevard Henri IV, CS89508, 34960 Montpellier cedex 2, France and the ^**Neurodégénérescence et Plasticité, INSERM EMI0108, CHU La Tronche, BP217, 38043 Grenoble, France

The host cell MAP kinase ERK-2 incorporated within human immunodeficiency virus type 1 particles plays a critical role in virus infectivity by phosphorylating viral proteins. Recently, a fraction of the virus incorporated late (L) domain-containing p6^gag protein, which has an essential function in the release of viral particles from the cell surface, was reported to be phosphorylated by an unknown virus-associated cellular protein kinase (Muller, B., Patschinsky, T., and Krausslich, H. G. (2002) J. Virol. 76, 1015–1024). The present study demonstrates the contribution of the MAP kinase ERK-2 in p6^gag phosphorylation. According to mutational analysis, a single ERK-2-phosphorylated threonine residue, belonging to a highly conserved phosphorylation MAP kinase consensus site, was identified at position 23 within p6^gag. Substitution by an alanine of the Thr²³ phosphorylable residue within the pNL4.3 molecular clone was found to decrease viral release from various cell types. As observed from electron microscopy experiments, most virions produced from this molecular clone remained incompletely separated from the host cell membrane with an immature morphology and displayed a reduced infectivity in single round infection experiments. Analysis of protein processing by Western blotting experiments revealed an incomplete Pr55^gag maturation and a reduction in the virion-associated reverse transcriptase proteins was observed that was not related to differences in intracellular viral protein expression. Altogether, these data suggest that phosphorylation of p6^gag protein by virus-associated ERK-2 is involved in the budding stage of HIV-1 life cycle.

Received for publication, December 2, 2003 , and in revised form, May 19, 2004.

^* This work was supported in part by the Centre National de la Recherche Scientifique (CNRS), the French agency against AIDS (ANRS), and the association "Ensemble contre le SIDA." The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Contributed equally to the results of this work.

^¶ Fellow from the French agency against AIDS (ANRS).

^|| Supported by a grant from the association "Ensemble contre le SIDA."

To whom correspondence should be addressed: UM1-CNRS UMR 5121, Institut de Biologie, 4 Bd Henri IV, CS89508, 34960 Montpellier cedex 2, France. Tel.: 33-4-67-60-86-60; Fax: 33-4-67-60-44-20; E-mail: laurence.briant{at}univ-montp1.fr.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				Y.-S. Chen, W.-H. Huang, S.-Y. Hong, Y.-G. Tsay, and P.-J. Chen ERK1/2-Mediated Phosphorylation of Small Hepatitis Delta Antigen at Serine 177 Enhances Hepatitis Delta Virus Antigenomic RNA Replication J. Virol., October 1, 2008; 82(19): 9345 - 9358. [Abstract] [Full Text] [PDF]

				E. Kuang, Q. Tang, G. G. Maul, and F. Zhu Activation of p90 Ribosomal S6 Kinase by ORF45 of Kaposi's Sarcoma-Associated Herpesvirus and Its Role in Viral Lytic Replication J. Virol., February 15, 2008; 82(4): 1838 - 1850. [Abstract] [Full Text] [PDF]

				L. J. Law, C. S. Ilkow, W.-P. Tzeng, M. Rawluk, D. T. Stuart, T. K. Frey, and T. C. Hobman Analyses of Phosphorylation Events in the Rubella Virus Capsid Protein: Role in Early Replication Events J. Virol., July 15, 2006; 80(14): 6917 - 6925. [Abstract] [Full Text] [PDF]

				M. G. Lyman, J. A. Randall, C. M. Calton, and B. W. Banfield Localization of ERK/MAP Kinase Is Regulated by the Alphaherpesvirus Tegument Protein Us2 J. Virol., July 15, 2006; 80(14): 7159 - 7168. [Abstract] [Full Text] [PDF]

				D. G. Nguyen, K. C. Wolff, H. Yin, J. S. Caldwell, and K. L. Kuhen "UnPAKing" Human Immunodeficiency Virus (HIV) Replication: Using Small Interfering RNA Screening To Identify Novel Cofactors and Elucidate the Role of Group I PAKs in HIV Infection J. Virol., January 1, 2006; 80(1): 130 - 137. [Abstract] [Full Text] [PDF]

				T. Fossen, V. Wray, K. Bruns, J. Rachmat, P. Henklein, U. Tessmer, A. Maczurek, P. Klinger, and U. Schubert Solution Structure of the Human Immunodeficiency Virus Type 1 p6 Protein J. Biol. Chem., December 30, 2005; 280(52): 42515 - 42527. [Abstract] [Full Text] [PDF]

				J. Modrof, K. Lymperopoulos, and P. Roy Phosphorylation of Bluetongue Virus Nonstructural Protein 2 Is Essential for Formation of Viral Inclusion Bodies J. Virol., August 1, 2005; 79(15): 10023 - 10031. [Abstract] [Full Text] [PDF]

				P. Rajendra Kumar, P. K. Singhal, M. R. K. Subba Rao, and S. Mahalingam Phosphorylation by MAPK Regulates Simian Immunodeficiency Virus Vpx Protein Nuclear Import and Virus Infectivity J. Biol. Chem., March 4, 2005; 280(9): 8553 - 8563. [Abstract] [Full Text] [PDF]

				S. M. Rue, J. W. Roos, P. M. Tarwater, J. E. Clements, and S. A. Barber Phosphorylation and Proteolytic Cleavage of Gag Proteins in Budded Simian Immunodeficiency Virus J. Virol., February 15, 2005; 79(4): 2484 - 2492. [Abstract] [Full Text] [PDF]