Work

Lipid-dependence of target membrane stability during influenza viral fusion

Year: 2018

Type: article

Abstract: ABSTRACT Although influenza kills about a half million people each year, even after excluding pandemics, there is only one set of antiviral drugs: neuraminidase inhibitors. By 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, depending upon 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 approximately −0.20 nm−1 fusion between influenza virus and target membrane is predominantly non-leaky while above that fusion is predominantly leaky, suggesting that influenza hemagglutinin (HA)-catalyzed topological conversion of target membranes during fusion is associated with a loss of membrane integrity.

Source: Journal of Cell Science

DOI: 10.1242/jcs.218321

Authors: Sourav Haldar, Elena Mekhedov, Chad D. McCormick, Paul S. Blank, Joshua Zimmerberg

Institution: Eunice Kennedy Shriver National Institute of Child Health and Human Development

Language: English

Topic: Lipid Membrane Structure and Behavior

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institutes of Health, National Institute of Child Health and Human Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NHLBI Division of Intramural Research