Open AccessEbola virus glycoprotein interacts with cholesterol to enhance membrane fusion and cell entry
Author(s) -
Jinwoo Lee,
Alex J. B. Kreutzberger,
Laura Odongo,
Elizabeth A. Nelson,
David A. Nyenhuis,
Volker Kiessling,
Binyong Liang,
David S. Cafiso,
Judith M. White,
Lukas K. Tamm
Publication year - 2021
Publication title -
nature structural and molecular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.448
H-Index - 270
eISSN - 1545-9993
pISSN - 1545-9985
DOI - 10.1038/s41594-020-00548-4
Subject(s) - endosome , lipid bilayer fusion , npc1 , ebola virus , glycoprotein , viral entry , microbiology and biotechnology , cell fusion , membrane glycoproteins , viral membrane , transmembrane protein , cell membrane , cholesterol , transmembrane domain , chemistry , fusion protein , virology , virus , biology , viral envelope , cell , membrane , biochemistry , viral replication , receptor , recombinant dna , gene
Cholesterol serves critical roles in enveloped virus fusion by modulating membrane properties. The glycoprotein (GP) of Ebola virus (EBOV) promotes fusion in the endosome, a process that requires the endosomal cholesterol transporter NPC1. However, the role of cholesterol in EBOV fusion is unclear. Here we show that cholesterol in GP-containing membranes enhances fusion and the membrane-proximal external region and transmembrane (MPER/TM) domain of GP interacts with cholesterol via several glycine residues in the GP2 TM domain, notably G660. Compared to wild-type (WT) counterparts, a G660L mutation caused a more open angle between MPER and TM domains in an MPER/TM construct, higher probability of stalling at hemifusion for GP2 proteoliposomes and lower cell entry of virus-like particles (VLPs). VLPs with depleted cholesterol show reduced cell entry, and VLPs produced under cholesterol-lowering statin conditions show less frequent entry than respective controls. We propose that cholesterol-TM interactions affect structural features of GP2, thereby facilitating fusion and cell entry.