Investigating the Impact of Cholesterol on GP41-Driven HIV Membrane Fusion

Membrane fusion is a critical step in HIV infection, allowing the virus envelope to merge with the host cell membrane and deliver genetic material. Cholesterol is believed to play a pivotal role in HIV fusion; however, the specific mechanism by which it facilitates membrane fusion remains poorly understood. Our molecular dynamics simulation study elucidates the dual role of cholesterol: it promotes GP41 aggregation by reducing the dimerization free energy and enhances the strengths of the protein-induced membrane curvatures. The free energy calculations reveal that by enhancing membrane curvatures, cholesterol significantly reduces the energy barriers and stabilizes the fusion intermediates. These findings highlight cholesterol's essential role in facilitating HIV entry and offer insights for potential antiviral strategies.