Influenza hemagglutinin drives viral entry via two sequential intramembrane mechanisms

Significance Viral proteins that accomplish membrane fusion between the virus and a host cell do two things: draw virus and host membranes together and act within these membranes to induce fusion. This second property is much less well understood than the first. We have used molecular dynamics simulations approximating influenza virus fusion to obtain a model of how influenza proteins promote fusion within interacting membranes. This model helps explain previous mutational data and new experiments. Viral fusion proteins have long been thought to curve and disorder membranes; we can now specify when and how this is accomplished. This provides a better fundamental understanding of viral entry and a basis for interpreting host defenses that act on membranes to interfere with infection.