Graves, Drayson2025-04-102025-04-102025-03-252025-03-25http://hdl.handle.net/1993/39002Human adenovirus (HAdV) is a collection of viral species (A through G) within the family adenoviridae that are associated with a wide variety of diseases including respiratory and gastrointestinal infections, as well as keratoconjunctivitis. Most infections tend to be mild and self-clearing, but certain species (HAdVs B and E especially) are much more dangerous than average, especially to children, the elderly, and the immunocompromised. Here I report my findings on two less-studied aspects of HAdV biology. First, I show that the smallest three splicing isoforms of the HAdV-C E1A protein are not properly generated when the E1A genomic region is supplied in trans, and that this reduces E1-deficient HAdV growth approximately twofold; an important discovery for generation of therapeutic HAdV vectors, as these are almost always E1-deficient. Second, I compare IFN resistance in HAdVs C (mild) and B (severe), revealing that HAdV-B is superior at preventing host cell ISG expression. I theorize that this may be in part due to a novel mechanism in which the virus sequesters away the host cell protein RuvBL1 to prevent its role in ISG expression. These results shed new light on two aspects of HAdV, both in terms of its role as a pathogen and as a therapeutic vector.engadenoviruse1avirology