Human norovirus infection is the leading cause of acute gastroenteritis, with an estimated 685
million cases per year worldwide. Luckily, the infection is transient with symptoms including
vomiting and diarrhea that typically last for only 24-48 hours, after which the virus is cleared from
the patient. However, the long-term implications of having experienced a Norovirus infection are
not clear. Using the Murine Norovirus (MNV) model in mice we found that a transient
gastrointestinal MNV colonization has a profound influence on the production of multiple
inflammatory mediators in the intestinal immune system. Because the intestinal immune system
controls systemic immunity, these intestinal alterations might influence susceptibility of the host to
subsequent diseases. Moreover, experiments in mice recently showed that intestinal ecosystem
alterations in pregnant mothers affects the intestinal immune system of the offspring. Therefore, in
this project we will carefully investigate the alterations that MNV provokes in the intestinal immune
system of its host, as well as in the intestine of the host’s offspring in case MNV colonizes during
pregnancy. In addition, we will investigate the underlying molecular mechanisms that Noroviruses
use to provoke these intestinal immunity alterations. Taken together, this project will elucidate how
a transient gastrointestinal viral colonization may have long-term or even next-generation effects on
host health.