Noroviruses are the leading cause of non-bacterial gastroenteritis in the world and are estimated to cause 267 million infections and 20,000 deaths each year. This virus causes severe diarrhea, nausea, and stomach pain.

Although often referred to as the “cruise ship” virus in the United States, noroviruses are an expensive and serious public health problem particularly among young children, the elderly, and immune-compromised patients. Now, in a new study published in Immunity this week, researchers from the Perelman School of Medicine at the University of Pennsylvania have used a mouse model to show that, even in immunized animals, noroviruses can escape the immune system and still spread by hiding out in an extremely rare type of cell in the gut.

“Current vaccines against norovirus have been ineffective despite eliciting strong antibody responses,” said senior author E. John Wherry, PhD, a professor of Microbiology and director of the Penn Institute for Immunology. “Understanding the unique norovirus characteristic of hiding from the host immune system may explain its biology and present opportunities to improve vaccines and therapeutics.”

While most infected people clear the virus within a few days, some individuals continue to shed virus for weeks to months after. Such persistently infected people may be a source of outbreaks, but it was unclear why the immune system fails to eliminate the virus in these cases.

 “The cruise ship outbreaks of norovirus are high profile, but it happens everywhere – daycare centers, eldercare facilities, and more,” said first author Vesselin T. Tomov, MD, PhD, an assistant professor of Gastroenterology. “Noroviruses can cause persistent infections, challenging the long-held view that they are transient pathogens.”

The Penn investigators defined and tracked T-cell responses in mice infected with either an acute or chronic strain of mouse norovirus to gain insight into mechanisms of viral clearance and persistence. At first, they hypothesized that persistent norovirus infection caused T cells to become exhausted rendering them non-functioning, similar to other chronic viral infections such as HIV or hepatitis C. To their surprise, however, T cells remained functional even after months of norovirus infection.

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