Lipid-dependence of target membrane stability during influenza viral fusion

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.