Research Overview

  • The influenza virus is a serious public health concern causing significant mortality and morbidity worldwide. The annual impact of which is largely determined by each strain’s ability to efficiently be transmitted from one host to another, or transmissibility, and the severity of the disease state caused by the virus, or virulence. While the interactions between viral and host proteins that determine transmissibility have been extensively studied, our understanding of the strain specific interactions that underlie virulence is extremely limited. One protein that facilitates viral evasion of the host immune response, and thus plays a critical role in modulating virulence, is the non-structural protein 1 (NS1). Not only does its absence attenuate influenza infection, certain variants also dramatically enhance virulence. NS1 is also considered to be a high valued target for the development of novel antivirals against influenza infection. Although many cellular proteins that interact with NS1 have been identified, a thorough structural and biophysical analysis of the strain dependent nature of these interactions is lacking. The knowledge gained by answering these questions will not only provide structural and biophysical insight into strain specific interactions that enhance virulence, but it will also guide the development of novel antivirals against influenza infection.

    The overall goal of my lab is to structurally and biochemically characterize the strain dependence of NS1 function through analysis of naturally occurring mutations in NS1. The rationale that underlies our research is that elucidating structure-function relationships between NS1 and its cellular interaction partners will provide critical insight into how influenza is able to evade the host immune response. To determine the strain dependent aspects of NS1 function, we will utilize a number of biophysical methods designed to interrogate the interaction between NS1 and host cell proteins. The primary method for determining and characterizing the interaction between NS1 and host proteins will be biomolecular nuclear magnetic resonance (NMR). For example, we will use an NMR technique known as chemical shift perturbation analysis to map intermolecular interface between NS1 and host cell proteins. Analysis of each interaction will include NS1 proteins derived from multiple strains of influenza to determine their dependence on strain. In addition, using multiple strains will identify naturally occurring mutations that are critical to the interactions being studied. Ultimately, this information will allow us to formulate further experiments using mutant recombinant influenza viruses to determine each naturally occurring mutation’s role in replication, the innate immune response, and pathogenicity.
  • Education And Training

  • Doctor of Philosophy in Veterinary Sciences / Veterinary Clinical Sciences, Louisiana State University System : Baton Rouge 2005
  • Full Name

  • Chad Petit