Protein-Lipid Interactions in a Full-Scale Influenza a Virion: Insight into Flu Seasonality

Abstract

The human influenza A virus exhibits seasonal infectivity in temperate regions, but there is still disagreement on the biophysical explanation. The recent publication of the lipidome of an influenza A virus provides compelling evidence that the virus buds from lipid rafts in the host plasma membrane, and that the virus is selectively enriched in cholesterol and sphingolipids beyond the plasma membrane raft from which it buds. These lipidomic details have allowed us to construct a full-scale computational model of the influenza A virion with a realistic lipid composition. We report preliminary findings on the lipid dynamics in these asymmetric viral envelopes containing the viral glycoproteins, hemagglutinin (HA) and neuraminidase (NA), and the M2 ion channel, using coarse-grained molecular dynamics simulations. Furthermore, there is currently only indirect evidence for an interaction between the M1 matrix protein and the influenza A glycoproteins, resulting in a degree of uncertainty in the amount of motion expected of the viral proteins. We have thus conducted simulations with both mobile and restrained viral proteins to assess the effect of viral protein mobility on the number, size and stability of lipid domains.