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

Friedrich M, Setz C, Hahn F, Matthaei A, Fraedrich K, Rauch P, Henklein P, Traxdorf M, Fossen T, Schubert U (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Viruses MDPI

Book Volume: 8

Pages Range: 117

Journal Issue: 4

DOI: 10.3390/v8040117

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.

Authors with CRIS profile

Melanie Setz Professur für Virologie Christian Setz Professur für Virologie Friedrich Hahn Professur für Virologie Maximilian Traxdorf Lehrstuhl für Hals-, Nasen- und Ohrenheilkunde Ulrich Schubert Professur für Virologie

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Involved external institutions

Charité - Universitätsmedizin Berlin DE Germany (DE) University of Bergen / Universitetet i Bergen NO Norway (NO)

How to cite

APA:

Friedrich, M., Setz, C., Hahn, F., Matthaei, A., Fraedrich, K., Rauch, P.,... Schubert, U. (2016). Glutamic Acid Residues in HIV-1 p6 Regulate Virus Budding and Membrane Association of Gag. Viruses, 8(4), 117. https://dx.doi.org/10.3390/v8040117

MLA:

Friedrich, Melanie, et al. "Glutamic Acid Residues in HIV-1 p6 Regulate Virus Budding and Membrane Association of Gag." Viruses 8.4 (2016): 117.

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