The host cell MAP kinase ERK-2 regulates viral assembly and release by phosphorylating the p6gag protein of HIV-1.

Abstract : 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 Thr(23) 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.
Type de document :
Article dans une revue
Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2004, 279 (31), pp.32426-34. 〈10.1074/jbc.M313137200〉
Liste complète des métadonnées

Littérature citée [35 références]  Voir  Masquer  Télécharger

http://www.hal.inserm.fr/inserm-00381846
Contributeur : Sandrine Fraboulet <>
Soumis le : mardi 19 juillet 2011 - 10:30:43
Dernière modification le : jeudi 11 janvier 2018 - 06:15:36
Document(s) archivé(s) le : samedi 3 décembre 2016 - 00:22:33

Fichier

 Accès restreint
Fichier visible le : jamais

Connectez-vous pour demander l'accès au fichier

Identifiants

Collections

UGA

Citation

Bénédicte Hemonnot, Christine Cartier, Bernard Gay, Sandra Rebuffat, Martine Bardy, et al.. The host cell MAP kinase ERK-2 regulates viral assembly and release by phosphorylating the p6gag protein of HIV-1.. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2004, 279 (31), pp.32426-34. 〈10.1074/jbc.M313137200〉. 〈inserm-00381846〉

Partager

Métriques

Consultations de la notice

259