tetano
Editor, Senior Moderator
J Cell Sci. 2018 Jul 2. pii: jcs.218321. doi: 10.1242/jcs.218321. [Epub ahead of print]
[h=1]Lipid-dependence of target membrane stability during influenza viral fusion.[/h] Haldar S[SUP]1[/SUP], Mekhedov E[SUP]1[/SUP], McCormick CD[SUP]1[/SUP], Blank PS[SUP]1[/SUP], Zimmerberg J[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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[SUP]-1[/SUP] 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.
[h=4]KEYWORDS:[/h] Fusion; Membrane; Poration; Spontaneous curvature; Virus
PMID: 29967032 DOI: 10.1242/jcs.218321
[h=1]Lipid-dependence of target membrane stability during influenza viral fusion.[/h] Haldar S[SUP]1[/SUP], Mekhedov E[SUP]1[/SUP], McCormick CD[SUP]1[/SUP], Blank PS[SUP]1[/SUP], Zimmerberg J[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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[SUP]-1[/SUP] 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.
[h=4]KEYWORDS:[/h] Fusion; Membrane; Poration; Spontaneous curvature; Virus
PMID: 29967032 DOI: 10.1242/jcs.218321