Noroviruses can escape the immune system by hiding out in rare gut cells



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

In the United States, Noroviruses often referred to as the “cruise ship” virus. Noroviruses are an expensive and serious public health problem particularly among young children, elders, and immune-compromised patients.

Current vaccines against norovirus ineffective, despite eliciting strong antibody responses, said, senior author E. John Wherry, director of the Penn Institute for Immunology.

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

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tracked T-cell responses in mice

Noroviruses can cause persistent infections, challenging the long-held view that they are transient pathogens. However, Penn investigators tracked T-cell responses in mice infected with an acute, chronic strain of mouse norovirus to gain insight into mechanisms of viral clearance and persistence. To their surprise, T cells remained functional even after months of norovirus infection.

The team then looked at the earliest stages of response by the immune system and found two phases to that response. During the initial days after infection, T cells reacted strongly to the virus and controlled it. After three days, T cells could no longer detect norovirus in 50 to 70 percent of the mice infected with the chronic strain.

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The researchers faced a paradox because the T cells responding to the virus appeared “ignorant” or “unable to see” the virus. To explain this problem, they hypothesized that actively multiplying norovirus sequestered somewhere in the gut out of reach of T cells.

Researchers found that norovirus hides specialized, ultra-rare cells of the gut lining. These cells act as mega factories for norovirus production, while allowing the virus to evade the immune system.

These findings might help to explain why norovirus vaccines tested limited effectiveness. And future vaccines would need to obtain immunity that acts very robust in the first three days after infection before the virus moves into hiding.

More infection: [Immunity]