Synchronized HIV assembly by tunable PIP2 changes reveals PIP2 requirement for stable gag anchoring

Frauke Mücksch, Vibor Laketa, Barbara Müller, Carsten Schultz, Hans Georg Kräusslich

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

HIV-1 assembles at the plasma membrane (PM) of infected cells. PM association of the main structural protein Gag depends on its myristoylated MA domain and PM PI(4,5)P2. Using a novel chemical biology tool that allows rapidly tunable manipulation of PI(4,5)P2 levels in living cells, we show that depletion of PI(4,5)P2 completely prevents Gag PM targeting and assembly site formation. Unexpectedly, PI(4,5)P2 depletion also caused loss of pre-assembled Gag lattices from the PM. Subsequent restoration of PM PI(4,5)P2 reinduced assembly site formation even in the absence of new protein synthesis, indicating that the dissociated Gag molecules remained assembly competent. These results reveal an important role of PI(4,5)P2 for HIV-1 morphogenesis beyond Gag recruitment to the PM and suggest a dynamic equilibrium of Gag-lipid interactions. Furthermore, they establish an experimental system that permits synchronized induction of HIV-1 assembly leading to induced production of infectious virions by targeted modulation of Gag PM targeting.

Original languageEnglish (US)
Article numbere25287
JournaleLife
Volume6
DOIs
StatePublished - Jun 2 2017

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Cell membranes
Cell Membrane
HIV
HIV-1
gag Gene Products
Morphogenesis
Virion
Restoration
Cells
Modulation
Association reactions
Lipids
Molecules

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Synchronized HIV assembly by tunable PIP2 changes reveals PIP2 requirement for stable gag anchoring. / Mücksch, Frauke; Laketa, Vibor; Müller, Barbara; Schultz, Carsten; Kräusslich, Hans Georg.

In: eLife, Vol. 6, e25287, 02.06.2017.

Research output: Contribution to journalArticle

Mücksch, Frauke ; Laketa, Vibor ; Müller, Barbara ; Schultz, Carsten ; Kräusslich, Hans Georg. / Synchronized HIV assembly by tunable PIP2 changes reveals PIP2 requirement for stable gag anchoring. In: eLife. 2017 ; Vol. 6.
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