Project 1: The fastidious human enteric adenoviruses are a leading cause of pediatric diarrhea but do not cause disease in other tissues. Research interests include the unique structural features of these enteric adenoviruses, how their structural features contribute to their intestinal tropism, how they enter intestinal cells and how their replication is blocked in other cells.
Project 2: Antiviral agents for the treatment of serious adenovirus infections. Human adenoviruses typically cause relatively mild, self-limiting infections but there are exceptions. Even immunocompetent hosts are susceptible to serious respiratory disease and to epidemic keratoconjunctivitis, a disease that affects the eye and can result in vision loss. At present, there are no antiviral agents approved for the treatment of adenovirus infections. Digoxin, a cardiotonic steroid that has been used for centuries to treat heart failure, the reduced yield of progeny virus ~10,000-fold at 24 hours post-infection. Subsequent time-course experiments showed that digoxin delayed but didn’t completely block virus replication though it did compromise the spread of the virus in cell cultures. In the context of disease, slowing the spread of the virus could be beneficial in giving the immune system more time to resolve the infection. Delayed and slower replication of the viral genome within infected cells may reflect the slower accumulation that we found for early transcripts that encode the viral DNA polymerase. Data thus far suggest that late functions, including packaging of the genome and/or virion assembly, may also be compromised. Experiments are ongoing to characterize the effects of digoxin on adenovirus replication and on the host cell, in preparation to test the clinical benefit of digoxin in vivo. An effective antiviral agent against adenoviruses that cause serious disease would alleviate considerable morbidity and mortality.
- MGY378H1 S
- MGY381H1 S
- MGY440H1 F
- MMG topic course (Virus-Cell Interactions)
- Teaching Award 2014 - Excellence in Undergraduate Laboratory Teaching in the Life Sciences
- Department of Laboratory Medicine and Pathobiology, University of Toronto