MHCII cross-presentation as a driver of CD4+ T cell responses to poxviruses

Viruses have evolved numerous strategies to interfere with the immune response. Here we compare how influenza virus and poxviruses (ectromelia mousepox and vaccinia) inhibit antigen presentation to T lymphocytes, the seminal event in beginning a specific immune response in all mammals. Our preliminary data show that influenza and poxviruses have separate and unique strategies for impeding antigen presentation and T lymphocyte activation. We plan to analyze how specific viral peptides are presented to CD4+ T lymphotyes and identity which cells are activated during a live infection. Our lab has identified a unique poxvirus protein (A35) that interferes with MHC class II antigen presentation to CD4+ T lymphocytes. We will analyze the amino acid differences in the sequences between the highly pathogenic mousepox sequence and the less virulent vaccinia A35 sequence to determine whether these sequences cause the differences in virulence between these viruses and to identify crucial amino acids for the A35 function. We will further investigate the mechanism of action of the A35 protein, studying its interactions with and effects on the endosomal proteins and endosomal compartment where it localizes. This research will elucidate mechanisms viruses use to successfully infect mammals and will thus identify drug targets and strategies for improved vaccine design.

Scholars @ ECU