HIV-1, the causative agent of AIDS buds from the plasma membrane to infect the target cell. It has been known that the HIV-1 Gag, the structural protein of HIV-1 binds to the head group of plasma membrane specific lipid phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2] and drives virus assembly process. Once complete, the virus buds from the plasma membrane and is ready to to infect another cell. Gag binding to the plasma membrane is an important and necessary step in the HIV-1 life cycle as mutations that abolish plasma membrane binding fails to produce virus.

In a study published in Journal of Virology, Olety et al, have found another determinant responsible for Gag binding to the plasma membrane. Employing an in-vitro assay system where protein binding can be visualized to giant unilamellar vesicles (GUV’s) or lipid membranes, the authors found that HIV-1 Gag binding to membranes not only depended on the head group of the lipid PI(4,5)P2 as previously known but its binding also depended on the type of fatty acids (or acyl chains) of the PI(4,5)P2 lipid.

Specifically, PI(4,5)P2 lipid that had oleoyl acyl chains (with unsaturated hydrogen bonds) supported HIV-1 Gag binding but HIV-1 Gag did not bind to membranes containing the same PI(4,5)P2 lipid but with palmitoyl acyl chains that lack any unsaturation. The authors here report that such a novel mechanism of protein binding to lipid membranes that depends not only on the head group but also on its acyl chain is novel and has not been reported before.

Interestingly, they also found that another well studied PI(4,5)P2 binding cellular protein (PHPLCδ1) does not depend on acyl chains and binds irrespective of the nature of acyl chains. They say that this novel property of membrane binding of HIV Gag that differs from cellular protein PHPLCδ1 might be might be an attractive target for developing drugs that specifically target HIV-1 Gag without affecting other cellular proteins.

http://jvi.asm.org/content/89/15/7861.abstract?sid=e6b4b13f-340f-49dc-80a8-e9253708c087