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How norovirus infections get their start

Researchers have identified how the highly contagious norovirus infection begins in mice.

There is no treatment or vaccine to prevent norovirus, the highly contagious gastrointestinal illness best known for spreading rapidly on cruise chips, in nursing homes, and in schools. Until now, scientists have understood little about how the infection gets started.

Researchers have shown, in mice, that the virus infects a rare type of intestinal cell called a tuft cell, so named because each cell sports a cluster of hairlike extensions on its surface. While tuft cells are few in number, the new findings indicate that once the virus strikes, tuft cells multiply it quickly to set off severe infections.

The findings suggest that targeting tuft cells with a vaccine or a drug may be a viable strategy for preventing or treating norovirus infections.

“Norovirus is one of the deadliest human pathogens that we know the least about,” says first author Craig B. Wilen, an instructor in pathology and immunology. “Of the viruses worldwide for which there are no antiviral drugs or vaccines, norovirus arguably kills the most people. This study provides a therapeutic avenue to explore.”

The virus causes severe vomiting and diarrhea that can develop suddenly. It’s shed in the feces and vomit—sometimes for months after symptoms resolve—and spreads through people-to-people contact, by touching contaminated surfaces and then the mouth, or eating contaminated food.

Human norovirus can’t be grown easily in a lab, so researchers choose to study it in mice.

“We were most surprised that the virus infects such a rare cell type and that even with so few cells infected, the infections can be intense and easily transmitted,” Wilen says. “In a single mouse, for example, maybe 100 cells will be infected, which is very few compared with other viruses such as the flu.”

Tuft cells are a type of epithelial cell that protrudes into the intestine. They are also known to detect parasitic and worm infections in the gut and trigger an immune response.

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Such infections can make infections worse and may explain why people in the developing world—where intestinal parasites and worm infections are more common—are more likely to die.

But, until now, scientists didn’t understand how norovirus could be linked to intestinal parasite and worm infections. The new study indicates that infections in the mice cause the number of tuft cells to increase by five- to tenfold, letting the norovirus replicate more efficiently.

Treating the mice with a powerful broad-spectrum antibiotic cocktail decreased the number of tuft cells and the risk of norovirus infection.

But, the antibiotics used in the study would not be practical to give to patients because they would deplete gut microbes that keep the body healthy, Wilen says.

Further, noroviruses tucked inside tuft cells are effectively hidden from the immune system, which could explain why some people continue to shed virus long after they are no longer sick.

These “healthy carriers” are thought to be the source of norovirus outbreaks, so understanding how the virus evades detection in these people could lead to better ways to prevent outbreaks.

Norovirus sickens almost 700 million people a year

“This raises important questions about whether human norovirus infects tuft cells and whether people who have chronic norovirus infections and continue to shed the virus long after infection do so because the virus remains hidden in tuft cells,” Wilen says.

“If that’s the case, targeting tuft cells may be an important strategy to eradicate the virus.”

The researchers report their findings in the journal Science.

Source: Washington University in St. Louis

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