Investigating the Role of Cytokines in Norovirus Pathogenesis

Sarah Tatum

Authors:  Sarah M. Tatum, Emily W. Helm, Stephanie M. Karst

Faculty Mentor:  Stephanie M. Karst

College:  College of Medicine


Norovirus is the most common cause of severe childhood diarrhea and a leading cause of acute gastroenteritis. Murine norovirus (MNV) has been used as a model system to study norovirus infection, but immunocompetent adult mice infected with MNV do not show the hallmark symptoms of norovirus infection. Our lab has recently developed a novel neonatal mouse model where genetically immunocompetent neonatal mice infected with acute MNV-1 develop norovirus-induced diarrhea that peaks at 48 hours post infection (hpi). Interestingly, upon infection with the genetically similar strains of persistent MNV-3 and persistent MNV-CR6, neonatal mice show attenuated disease. To investigate whether differential induction of cytokines affects virulence, we harvested the small intestines and colons of neonatal mice at 24- and 48- hpi. We extracted RNA from the tissues and determined host cytokine expression in mock, MNV-1, MNV-3, and MNV-CR6 infected mice. Although most cytokines tested did not reach detectable levels following MNV infection, we did find a significant difference in the production of TNF-α and IL-1β between virus strains. As the virulent MNV-1 strain induced higher expression than the attenuated MNV-3 or MNV-CR6, future studies will examine the role of these two cytokines on the severity of norovirus-induced disease.

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6 Responses
  1. Drew Fletcher

    Great job Sarah! My question is, did you find any reason that the incidence of diarrhea in the MNV-3 strain is greater than the MNV-CR6 strain. Also, would cytokine induction differences between these strains be clinically relevant?