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Viruses. 2016 Apr 25;8(4):117. doi: 10.3390/v8040117.

Glutamic Acid Residues in HIV-1 p6 Regulate Virus Budding and Membrane Association of Gag.

Author information

1
Institute of Virology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen 91054, Germany. Melanie.Friedrich@viro.med.uni-erlangen.de.
2
Institute of Virology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen 91054, Germany. Christian.Setz@viro.med.uni-erlangen.de.
3
Institute of Virology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen 91054, Germany. Friedrich.Hahn@viro.med.uni-erlangen.de.
4
Institute of Virology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen 91054, Germany. Alina.Matthaei@viro.med.uni-erlangen.de.
5
Institute of Virology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen 91054, Germany. Kirsten.Fraedrich@viro.med.uni-erlangen.de.
6
Institute of Virology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen 91054, Germany. Pia.Rauch@viro.med.uni-erlangen.de.
7
Institute of Biochemistry, Charité Universitätsmedizin-Berlin, Berlin 10117, Germany. Petra.Henklein@charite.de.
8
Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen 91054, Germany. maximilian.traxdorf@uk-erlangen.de.
9
Department of Chemistry and Center for Pharmacy, University of Bergen, Bergen N-5007, Norway. Torgils.Fossen@kj.uib.no.
10
Institute of Virology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen 91054, Germany. Ulrich.Schubert@viro.med.uni-erlangen.de.

Abstract

The HIV-1 Gag p6 protein regulates the final abscission step of nascent virions from the cell membrane by the action of its two late (L-) domains, which recruit Tsg101 and ALIX, components of the ESCRT system. Even though p6 consists of only 52 amino acids, it is encoded by one of the most polymorphic regions of the HIV-1 gag gene and undergoes various posttranslational modifications including sumoylation, ubiquitination, and phosphorylation. In addition, it mediates the incorporation of the HIV-1 accessory protein Vpr into budding virions. Despite its small size, p6 exhibits an unusually high charge density. In this study, we show that mutation of the conserved glutamic acids within p6 increases the membrane association of Pr55 Gag followed by enhanced polyubiquitination and MHC-I antigen presentation of Gag-derived epitopes, possibly due to prolonged exposure to membrane bound E3 ligases. The replication capacity of the total glutamic acid mutant E0A was almost completely impaired, which was accompanied by defective virus release that could not be rescued by ALIX overexpression. Altogether, our data indicate that the glutamic acids within p6 contribute to the late steps of viral replication and may contribute to the interaction of Gag with the plasma membrane.

KEYWORDS:

">l-domains; ALIX; ESCRT; Gag p6; HIV-1; Tsg101; membrane association; ubiquitination; virus budding

PMID:
27120610
PMCID:
PMC4848609
DOI:
10.3390/v8040117
[Indexed for MEDLINE]
Free PMC Article

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