The devil is in the details: towards a mechanistic understanding of molecular interactions between host and influenza virus (Virtual)
Dr. Jae-Hyun Cho, Department of Biochemistry and Biophysics, Texas A&M
Host: Dr. Venditti
The 1918 influenza A virus (IAV) caused the worst flu pandemic (a. k. a., Spanish flu) in human history. Since then, the influenza virus has remained a major threat to public health. Nonstructural protein 1 (NS1) is a major virulence factor of influenza viruses and is considered a key player in the high virulence of 1918 IAV. NS1 interferes with host innate immune responses by interacting with a number of host proteins such as RIG-I, CPSF-30, and PI3K. Our lab focuses on the interaction between the host p85β subunit of PI3K (phosphoinositide 3 kinase) and NS1 proteins of different IAV strains, including 1918 IAV. I will first present the molecular recognition mechanism by which 1918 NS1 hijacks human CRK and PI3K. Then, I will present our recent work on the molecular evolution of NS1. The cryptic mutation is a hidden mutation that can make phenotypic effects only when combined with other mutations. However, it can have a substantial influence on molecular evolution. So, cryptic mutations have attracted broad interest, but their molecular basis is poorly understood. We have found cryptic mutations have reshaped the molecular energy landscape of NS1 since 1918. Overall, our data show that cryptic mutations can affect a wide range of molecular properties of NS1, such as protein dynamics and thermodynamic driving force for binding to p85, without affecting the phenomenological function.