Mathematical model of influenza A evolution with HA protein stability

Influenza A H3N2 displays a tremendous capacity to adapt and evolve in response to pressure from host immune systems. The mutations that aid in immune system evasion are thought to occur largely in the viral antigen hemagglutinin (HA). Nucleoprotein (NP) is another protein of influenza A that is under significantly less selection pressure than HA. It has been shown that substitutions in NP are constrained by NP stability. That is, certain substitutions that decrease stability, but otherwise increase fitness, only occur in tandem with others that increase NP stability. In this project, we formulate a phylodynamics model of viral evolution for influenza A that incorporates HA protein stability. Our model tracks host individuals that are, respectively, infected, have strain-transcending immunity, or have lifelong antibodies against each specific strain. Our formulation also includes salient biological features such as cross-immunity between closely related strains. We show that important novel features emerge due to the inclusion of HA protein stability in our model. We characterize these properties through multiple approaches, illustrating the significance of protein stability in influenza A models.