Synchronized HIV assembly by tunable PIP<sub>2</sub> changes reveals PIP<sub>2</sub> requirement for stable Gag anchoring.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 28574338.
- Also identified by DOI 10.7554/eLife.25287 and PMC identifier 5495570.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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)P<sub>2</sub>. Using a novel chemical biology tool that allows rapidly tunable manipulation of PI(4,5)P<sub>2</sub> levels in living cells, we show that depletion of PI(4,5)P<sub>2</sub> completely prevents Gag PM targeting and assembly site formation. Unexpectedly, PI(4,5)P<sub>2</sub> depletion also caused loss of pre-assembled Gag lattices from the PM. Subsequent restoration of PM PI(4,5)P<sub>2</sub> 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)P<sub>2</sub> 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.
Medical subject headings
- Cell Membrane
- HIV-1
- Phosphatidylinositol 4,5-Diphosphate
- Virus Assembly
- gag Gene Products, Human Immunodeficiency Virus