title: Nothing to sneeze at: a dynamic and integrative computational model of an influenza A virion.
abstract: The influenza virus is surrounded by an envelope composed of a lipid bilayer and integral membrane proteins. Understanding the structural dynamics of the membrane envelope provides biophysical insights into aspects of viral function, such as the wide-ranging survival times of the virion in different environments. We have combined experimental data from X-ray crystallography, nuclear magnetic resonance spectroscopy, cryo-electron microscopy, and lipidomics to build a model of the intact influenza A virion. This is the basis of microsecond-scale coarse-grained molecular dynamics simulations of the virion, providing simulations at different temperatures and with varying lipid compositions. The presence of the Forssman glycolipid alters a number of biophysical properties of the virion, resulting in reduced mobility of bilayer lipid and protein species. Reduced mobility in the virion membrane may confer physical robustness to changes in environmental conditions. Our simulations indicate that viral spike proteins do not aggregate and thus are competent for multivalent immunoglobulin G interactions.
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Tyler
authors.initials: T
authors.lastname: Reddy
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: David
authors.initials: D
authors.lastname: Shorthouse
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Parton
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Jefferys
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Philip W
authors.initials: PW
authors.lastname: Fowler
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Chavent
authors.affiliation: Institut de Biologie Physico-Chimique, Centre National de la Recherche Scientifique, UPR9080, Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Baaden
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK. Electronic address: mark.sansom@bioch.ox.ac.uk.
authors.forename: Mark S P
authors.initials: MSP
authors.lastname: Sansom
mesh_terms: D004058:Diffusion; D054884:Host-Pathogen Interactions; D006801:Humans; D009980:Influenza A virus / Q000737:chemistry / Q000648:ultrastructure*; D008055:Lipids / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D011991:Receptors, Virus / Q000737:chemistry; D014771:Virion / Q000737:chemistry / Q000648:ultrastructure*; D053585:Virus Attachment
chemical_list: D008055:Lipids; D011991:Receptors, Virus