Influenza A and B viruses are responsible for high levels of morbidity and mortality in the human population every year. Influenza C virus infection causes a mild upper respiratory disease in humans, with a seroprevalence of over 90 percent in the adult human population. This research proposal aims to study and characterize the influenza C virus life cycle by investigating the CM2 and the newly identified p31 viral proteins. The CM2 protein is believed to be the influenza C virus homolog of the influenza A virus M2 protein, a known ion channel that aids in the dissassembly of influenza A virus during entry into susceptible cells. I will characterize the effect of CM2 on the intracellular transport of integral membrane glycoproteins, as well as the Golgi morphology of CM2 expressing cells. Site-directed mutagenesis will be used in an attempt to disrupt the biological activity of CM2 without perturbing the oligomerization and surface transport of the protein. Whole cell patch-clamping of CM2 expressing eukaryotic cells will be performed in order to identify and characterize any potential ion channel activity of CM2. Finally, the pathway and signals involved in influenza C virus p31 protein degradation will be investigated. These studies should significantly further our understanding of the influenza C virus life cycle, and provide new insights into virus-host cell interactions.
|Takeda, Makoto; Pekosz, Andrew; Shuck, Kevin et al. (2002) Influenza a virus M2 ion channel activity is essential for efficient replication in tissue culture. J Virol 76:1391-9|
|Pekosz, A; Lamb, R A (2000) Identification of a membrane targeting and degradation signal in the p42 protein of influenza C virus. J Virol 74:10480-8|