HIV-1 gag recruits PACSIN2 to promote virus spreading

Sergei Popov, Elena Popova, Michio Inoue, Yuanfei Wu, Heinrich Göttlinger

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

The p2b domain of Rous sarcoma virus (RSV) Gag and the p6 domain of HIV-1 Gag contain late assembly (L) domains that engage the ESCRT membrane fission machinery and are essential for virus release. We now show that the PPXY-type RSV L domain specifically recruits the BAR domain protein PACSIN2 into virus-like particles (VLP), in addition to the NEDD4-like ubiquitin ligase ITCH and ESCRT pathway components such as TSG101. PACSIN2, which has been implicated in the remodeling of cellular membranes and the actin cytoskeleton, is also recruited by HIV-1 p6 independent of its ability to engage the ESCRT factors TSG101 or ALIX. Moreover, PACSIN2 is robustly recruited by NEDD4-2s, a NEDD4-like ubiquitin ligase capable of rescuing HIV-1 budding defects. The NEDD4-2s–induced incorporation of PACSIN2 into VLP correlated with the formation of Gag-ubiquitin conjugates, indicating that PACSIN2 binds ubiquitin. Although PACSIN2 was not required for a single cycle of HIV-1 replication after infection with cell-free virus, HIV-1 spreading was nevertheless severely impaired in T cell lines and primary human peripheral blood mononuclear cells depleted of PACSIN2. HIV-1 spreading could be restored by reintroduction of wild-type PACSIN2, but not of a SH3 domain mutant unable to interact with the actin polymerization regulators WASP and N-WASP. Overall, our observations indicate that PACSIN2 promotes the cell-to-cell spreading of HIV-1 by connecting Gag to the actin cytoskeleton.

Original languageEnglish
Pages (from-to)7093-7098
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number27
DOIs
Publication statusPublished - 2018 Jul 3

Keywords

  • Gag
  • HIV-1
  • PACSIN2
  • Ubiquitin
  • Virus spreading

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'HIV-1 gag recruits PACSIN2 to promote virus spreading'. Together they form a unique fingerprint.

Cite this