Nothing to sneeze at: a dynamic and integrative computational model of an influenza A virion

Tyler Reddy , David Shorthouse , Daniel L Parton , Elizabeth Jefferys , Philip W Fowler (1) , Matthieu Chavent , Marc Baaden (2) , Mark S P Sansom

1 Division of Applied Medicine, Institute of Medical Sciences
2 LBT (UPR_9080) - Laboratoire de biochimie théorique [Paris]

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.

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.

Mots clés: Influenza A virus; Virion

Domaines: Sciences du Vivant [q-bio]

Tyler Reddy, David Shorthouse, Daniel L Parton, Elizabeth Jefferys, Philip W Fowler, et al.. Nothing to sneeze at: a dynamic and integrative computational model of an influenza A virion. Structure, 2015, 23 (3), pp.584-97. ⟨10.1016/j.str.2014.12.019⟩. ⟨hal-01230763⟩