Virus is one of the largest global health concerns. The ability of virus to rapidly evolve underlies the challenge to achieve a virus-free world. The two major problems are 1) immune evasion, which can lead to vaccine escape, and 2) host jump, which can lead to pandemic. Fortunately, not all viral mutations have a deleterious consequence to public health. Most viral mutations disrupt protein functions that are essential in the virus life cycle. Therefore, a significant portion of the viral genome is under strong evolutionary constraints. Our research interest is to characterize virus evolution, including both positive selection pressures (immune evasion and host adaptation) and negative selection pressures (virus-host molecular interactions), from biophysical and biochemical perspectives. While our main focus has been on influenza virus, we occasionally work on other viruses such as HIV, HCV, and SARS-CoV-2. Ongoing research directions include the followings:

Arms race between antibody response and virus

Antibodies are generated during virus infection or vaccination. While antibodies can offer protection against viral infection, virus can mutate to escape antibody response. As a result, there is a constant arms race between antibody response and virus. Our research aims to understand how affinity and breadth are developed during antibody evolution (Wu et al. 2017), as well as how virus escapes antibody response (Wu et al. 2020). This research direction provides important insight into vaccine design.

Evolutionary constraints of influenza virus

The evolution of influenza virus is functionally constrained since viral proteins possess many functions that are essential to the virus life cycle. Our research aims to investigate the mechanistic basis of these functional constraints, how they vary among different viral strains (Wu et al. 2020), and how they change over time (Wu et al. 2019). This research direction helps detail the molecular mechanisms of influenza pathogenesis, diversification, and host jump.

Egg adaptation of influenza virus

The effectiveness of the seasonal influenza vaccine is quite low, especially for H3N2 subtype. One major problem is the egg-based vaccine production process. Although passaging human influenza virus in embryonated chicken eggs is a highly cost-effective method for vaccine production, it often leads to the emergence of egg-adaptive mutations, which may alter the antigenicity of the virus. Our research aims to characterize the biophysical basis of antigenic alternation due to egg-adaptive mutations (Wu et al. 2017), as well as the genetic interactions between different egg-adaptive mutations (Wu et al. 2019). This research direction is informative for influenza vaccine strain selection.