Influenza membrane fusion is sensitive to endosomal lipids but robust to membrane curvature.

Abstract

Influenza virus infects cells via membrane fusion to the interior of endosomes. Endosomal membranes differ in their physical properties from the plasma membrane, most notably in curvature and membrane composition. We have employed single-virus microscopy to examine both lipid and content mixing between influenza virions and synthetic membranes of defined curvature and composition to test how these properties affect influenza entry. We find that influenza fusion is uncorrelated with single-vesicle membrane curvature. However, the endosomal lipid bis(monoacylglycero)phosphate does modulate the efficiency of influenza fusion to liposomes. Most interestingly, this effect is seen only on full fusion, not on lipid mixing, and only on efficiency, not on kinetics. We thus hypothesize that BMP lipids are an important permissive factor for endosomal entry and that they modulate alternative pathways in fusion mechanism.