HIV-1 Gag engages components of the ESCRT (endosomal sorting complex required for transport) pathway via so-called L (late-assembly) domains to promote virus budding. Specifically, the PTAP (Pro-Thr-Ala-Pro)-type primary L domain of HIV-1 recruits ESCRT-I by binding to Tsg101 (tumour susceptibility gene 101), and an auxiliary LYPXnL (Leu-Tyr-Pro-Xaan-Leu)-type L domain recruits the ESCRT-III-binding partner Alix [ALG-2 (apoptosis-linked gene 2)-interacting protein X]. The structurally related CHMPs (charged multivesicular body proteins), which form ESCRT-III, are kept in an inactive state through intramolecular interactions, and become potent inhibitors of HIV-1 budding upon removal of an autoinhibitory region. In the absence of the primary L domain, HIV-1 budding is strongly impaired, but can be efficiently rescued through the overexpression of Alix. This effect of Alix depends on its ability to interact with CHMP4, suggesting that it is the recruitment of CHMPs that ultimately drives virus release. Surprisingly, HIV-1 budding defects can also be efficiently corrected by overexpressing Nedd (neural-precursor-cell-expressed developmentally down-regulated) 4-2s, a member of a family of ubiquitin ligases previously implicated in the function of PPXY (Pro-Pro-Xaa-Tyr)-type L domains, which are absent from HIV-1. At least under certain circumstances, Nedd4-2s stimulates the activity of PTAP-type L domains, raising the possibility that the ubiquitin ligase regulates the activity of ESCRT-I.
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February 2009
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Conference Article|
January 20 2009
The ESCRT pathway and HIV-1 budding
Yoshiko Usami;
Yoshiko Usami
*Program in Gene Function and Expression, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, U.S.A.
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Sergei Popov;
Sergei Popov
*Program in Gene Function and Expression, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, U.S.A.
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Elena Popova;
Elena Popova
*Program in Gene Function and Expression, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, U.S.A.
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Michio Inoue;
Michio Inoue
*Program in Gene Function and Expression, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, U.S.A.
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Winfried Weissenhorn;
Winfried Weissenhorn
†Unit for Virus Host Cell Interaction, UMR 5233 UJF-EMBL-CNRS, 6 rue Jules Horowitz, 38042 Grenoble, France
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Heinrich G. Göttlinger
Heinrich G. Göttlinger
1
*Program in Gene Function and Expression, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, U.S.A.
1To whom correspondence should be addressed (email heinrich.gottlinger@umassmed.edu).
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Publisher: Portland Press Ltd
Received:
July 23 2008
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2009 Biochemical Society
2009
Biochem Soc Trans (2009) 37 (1): 181–184.
Article history
Received:
July 23 2008
Citation
Yoshiko Usami, Sergei Popov, Elena Popova, Michio Inoue, Winfried Weissenhorn, Heinrich G. Göttlinger; The ESCRT pathway and HIV-1 budding. Biochem Soc Trans 1 February 2009; 37 (1): 181–184. doi: https://doi.org/10.1042/BST0370181
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