Multimerizable HIV Gag derivative binds to the liquid-disordered phase in model membranes

Area of Science:

• Virology
• Biophysics
• Cell Biology

Background:

• HIV assembly relies on the Gag polyprotein interacting with the inner plasma membrane leaflet.
• A prevailing hypothesis suggests Gag induces and associates with lipid raft-like domains for viral budding.
• Lipid rafts are typically proposed as microdomains within the outer leaflet of the plasma membrane.

Purpose of the Study:

• To investigate the interaction of a multimerizable Gag derivative with a model membrane system mimicking the inner plasma membrane leaflet.
• To test the hypothesis that Gag preferentially associates with and induces raft-like domains during HIV assembly.

Main Methods:

• Utilized a minimal in vitro system with a domain-forming model membrane.
• Analyzed the interaction of a Gag derivative, triggered for multimerization, with the model membrane.
• Investigated the role of multimerization, myristoylation, and phosphatidylinositol 4,5-bisphosphate in Gag-membrane binding.

Main Results:

• The Gag derivative bound to the membrane only when multimerized, myristoylated, and in the presence of phosphatidylinositol 4,5-bisphosphate.
• Unexpectedly, the multimerized Gag derivative was largely excluded from ordered membrane domains.
• This exclusion challenges the simple model of Gag-induced lipid raft accumulation.

Conclusions:

• The mechanism of membrane reorganization during HIV assembly is more complex than direct preferential binding to ordered lipid domains.
• HIV Gag's interaction with the membrane may involve intricate biophysical forces or additional protein factors.
• Further research is needed to elucidate the precise molecular mechanisms driving HIV particle formation at the plasma membrane.