Authors: Erin Kirsche, Alexa Roth, Emily Helm, Jonathan Smith, Stephanie Karst
Faculty Mentor: Stephanie Karst
College: College of Medicine
Noroviruses are the leading cause of severe childhood diarrhea worldwide but the mechanisms by which they cause disease are unknown. Murine norovirus (MNV) is a suitable model to study norovirus pathogenesis in a natural host since it causes acute self-resolving diarrhea in neonatal mice. Importantly, virulence in neonatal mice positively correlates with the ability of a given MNV strain to replicate in lymphocytes and previous work in the lab has revealed that the MNV capsid protein VP1 regulates lymphocyte infection. There are 18 amino acid differences in VP1 when comparing a virulent strain to attenuated strains. Using a molecular approach, we engineered mutations in the virulent virus at these positions to test their contribution to regulating lymphocyte replication efficiency and the ability to cause diarrhea in neonatal mice. Thus far, I have identified one residue that regulates lymphocyte infection in vitro but does not regulate disease in vivo. Although this preliminary result does not support my hypothesis that lymphocyte infection is key to disease induction, I will continue to test the other recombinant viruses I have engineered and will also begin evaluating the role of other virus proteins in determining virulence.