Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Microbiology and Immunology

Supervisor

Mymryk, Joe

Abstract

When challenged by viral DNA, the cytoplasmic DNA sensor cyclic GMP-AMP synthase (cGAS) signals through the adaptor protein stimulator of interferon genes (STING) to induce a primary type I IFN response. Studies from recent years have also revealed shared architecture between metabolism and innate immunity. Viruses have evolved to counteract these mechanisms. Human adenovirus (HAdV) early region 1A (E1A) protein antagonizes the cGAS-STING pathway to prevent an innate immune response by physically interacting with STING. I hypothesize that the interaction between E1A and STING is mediated through several motifs and involves ribosomal protein S6 kinase beta-1 (S6K1). Using a series of co-immunoprecipitation assays, I determined that the interaction between STING and HAdV E1A is conserved and mediated through the E1A N-terminus region. I also found that E1A physically interacts with S6K1 and ribosomal protein S6 (RPS6). Further studies will reveal the biological function of these interactions.

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