The ESCRT pathway and HIV-1 budding

Yoshiko Usami, Sergei Popov, Elena Popova, Michio Inoue, Winfried Weissenhorn, Heinrich G. Göttlinger

Research output: Contribution to journalArticlepeer-review

82 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)181-184
Number of pages4
JournalBiochemical Society Transactions
Volume37
Issue number1
DOIs
Publication statusPublished - 2009

Keywords

  • ALG-2 (apoptosis-linked gene 2)-interacting protein X (Alix)
  • Autoinhibition
  • Endosomal sorting complex required for transport (ESCRT)
  • HIV-1
  • Neural-precursor-cell-expressed developmentally down-regulated 4 (Nedd4)
  • Virus budding

ASJC Scopus subject areas

  • Biochemistry

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