Life Sciences Commons^™

Characterizing The Interaction Between Human Adenovirus E1a And Sting, Jessica Hill

Electronic Thesis and Dissertation Repository

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 …

Characterizing The Interaction Between Human Adenovirus E1a And The Transcriptional Repressor Bs69, Ali Zhang

Electronic Thesis and Dissertation Repository

Protein products of the Early Region 1A (E1A) gene in human adenovirus 5 (HAdV-5) are the first viral proteins expressed upon adenovirus infection. E1A disrupts many cellular physiological events by binding to and regulating an impressive number of host factors. Of particular interest is BS69, a repressor of E1A transactivation. Due to the strong interaction observed between E1A and BS69, I hypothesize that these two proteins function together to disrupt gene expression within an infected cell.

Using in silico modelling and a series of yeast two-hybrid assays, I determined that residues 112-119 of HAdV-5 E1A is the minimal interacting region …