Lateral Membrane Heterogeneity Regulates Viral-Induced Membrane Fusion during HIV Entry

Abstract

Sphingomyelin- and cholesterol- enriched membrane domains, commonly referred to as “rafts” play a crucial role in a large number of intra- and intercellular processes. Recent experiments suggest that not only the volumetric inhomogeneity of lipid distribution in rafts, but also the arrangement of the 1D boundary between the raft and the surrounding membrane is important for the membrane-associated processes. The reason is that the boundary preferentially recruits different peptides, such as HIV (human immunodeficiency virus) fusion peptide. In the present work, we report a theoretical investigation of mechanisms of influence of the raft boundary arrangement upon virus-induced membrane fusion. We theoretically predict that the raft boundary can act as an attractor for viral fusion peptides, which preferentially distribute into the vicinity of the boundary, playing the role of ‘line active components’ of the membrane (‘linactants’). We have calculated the height of the fusion energy barrier and demonstrated that, in the case of fusion between HIV membrane and the target cell, presence of the raft boundary in the vicinity of the fusion site facilitates fusion. The results we obtained can be further generalized to be applicable to other enveloped viruses.

Single-cell glycolytic activity regulates membrane tension and HIV-1 fusion

“…First, it has been shown that lipid-ordered (i.e. cholesterol-laden) and lipid-disordered membrane domains (also termed raft boundaries) can act as an attractor for HIV Env [29,72]. Both experimental and theoretical studies show that the presence of raft boundaries in the vicinity of HIV-1 entry sites reduces the energy barrier required to perform virus-cell fusion [21].…”

Membrane Elastic Deformations Modulate Gramicidin A Transbilayer Dimerization and Lateral Clustering

“…Because the energy functional (Eq. 1) could be minimized for different peptide configurations (boundary conditions), the developed formalism is applicable for the description of a large variety of membrane proteins, including amphipathic peptides (37)(38)(39)(40) and channels.…”

Membrane Rafts: Portals for Viral Entry

“…Moreover, the presence of Lo domains in the cell membrane increases the overall fusion kinetics ( Yang et al, 2016 , 2017 ). The raft boundary can act as an attractor for viral fusion peptides ( Molotkovsky et al, 2018 ).…”