Open AccessLipid-dependence of target membrane stability during influenza viral fusion
Author(s) -
Sourav Haldar,
Elena Mekhedov,
Chad D. McCormick,
Paul S. Blank,
Joshua Zimmerberg
Publication year - 2018
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.218321
Subject(s) - lipid bilayer fusion , membrane , membrane curvature , biology , neuraminidase , fusion , viral membrane , vesicle , neuraminidase inhibitor , biophysics , lipid bilayer , virus , virology , microbiology and biotechnology , biochemistry , viral envelope , covid-19 , medicine , linguistics , philosophy , disease , pathology , infectious disease (medical specialty)
While influenza kills about a half million people each year, even after excluding pandemics, there is only one set of antiviral drugs: neuraminidase inhibitors. Using a new approach utilizing giant unilamellar vesicles and infectious X-31 influenza virus and testing for the newly identified pore intermediate of membrane fusion, we observed ∼30 - 87 % poration as a function of lipid composition. Testing the hypothesis that spontaneous curvature (SC) of the lipid monolayer controls membrane poration, our Poisson model and Boltzmann energetic considerations suggest a transition from a leaky to a non-leaky fusion pathway depending on the SC of the target membrane. When the target membrane SC is below∼-0.20 nm−1 fusion between influenza virus and target membrane is predominantly non-leaky while above that fusion is predominantly leaky, suggesting that HA catalyzed topological conversion of target membranes during fusion is associated with a loss of membrane integrity.