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Updated: Mar 1, 2026
08:21
Visualization of HIV-1 Gag Binding to Giant Unilamellar Vesicle GUV Membranes
Published on: July 28, 2016
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Synchronized HIV assembly by tunable PIP2 changes reveals PIP2 requirement for stable Gag anchoring
Frauke Mücksch1, Vibor Laketa1,2, Barbara Müller1
1Department of Infectious Diseases, Virology, University Hospital Heidelberg, Heidelberg, Germany.
Elife
|June 3, 2017
Summary
Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is crucial for human immunodeficiency virus type 1 (HIV-1) assembly. Modulating PI(4,5)P2 levels controls Gag protein targeting and HIV-1 morphogenesis.
Area of Science:
- Molecular Virology
- Cell Biology
- Chemical Biology
Background:
- HIV-1 assembly occurs at the plasma membrane (PM) of infected cells.
- The main structural protein, Gag, requires its myristoylated MA domain and PM PI(4,5)P2 for PM association.
Purpose of the Study:
- To investigate the role of PI(4,5)P2 in HIV-1 Gag targeting and assembly.
- To explore the dynamic regulation of Gag-lipid interactions during viral morphogenesis.
Main Methods:
- Utilized a novel chemical biology tool for rapid, tunable manipulation of PI(4,5)P2 levels in living cells.
- Observed Gag PM targeting, assembly site formation, and Gag lattice dynamics under varying PI(4,5)P2 conditions.
Main Results:
- PI(4,5)P2 depletion completely inhibited Gag PM targeting and assembly site formation.
- Unexpectedly, PI(4,5)P2 depletion also led to the dissociation of pre-formed Gag lattices from the PM.
- Restoration of PI(4,5)P2 reinduced assembly site formation, indicating retained Gag assembly competence.
Conclusions:
- PI(4,5)P2 plays a critical role in HIV-1 morphogenesis beyond initial Gag recruitment.
- Gag-lipid interactions at the PM are dynamically regulated.
- Established a system for synchronized HIV-1 assembly induction via PI(4,5)P2 modulation.
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