Researchers Discover Bile Acids Activate Endocytosis and Noroviruses Need Them to Invade Cells

Researchers Discover Bile Acids Activate Endocytosis and Noroviruses Need Them to Invade Cells

Noroviruses are the main cause of diarrhea and acute gastroenteritis worldwide. Noroviruses are highly contagious and are responsible for approximately 21 million cases of acute gastroenteritis in the United States each year. They are responsible for around 800 deaths in the U.S each year. Despite being so common, little was known about how the viruses infect humans until recently.

New research conducted by researchers at the Baylor College of Medicine has shed further light on how noroviruses invade cells. A 2018 study showed the viruses target tuft cells in the small intestine and invade the cells where they replicate and cause the symptoms of gastroenteritis.

Previous studies by the researchers established that bile was required for noroviruses to invade cells, but it was not known exactly what components of bile were promoting infection of cells in the small intestine.

The study was conducted on enteroids, which are physiologically active groups of cells that serve as a laboratory model of the small intestine. The enteroids consist of epithelial cells that have similar properties to the human small intestine, including the ability to support norovirus growth.

In their study, the researchers found that bile acids stimulate endocytosis, the process of incorporating extracellular material inside cells. The role bile acids play in stimulating endocytosis had not previously been reported. Bile acids are produced by the liver and help the body digest fats.

Noroviruses rely on bile acids and ceramide, a waxy lipid molecule present in high quantities in cell membranes and bile, to invade cells. The researchers found that these compounds are required for the noroviruses to invade cells in the small intestine. Once inside the cells they replicate and cause gastroenteritis symptoms.

This makes perfect sense for a food-borne virus. When food is ingested, it stimulates the production of bile which is necessary for digestion. Norovirus essentially piggybacks the endocytosis to get inside cells.

The findings suggest that it may be possible to reduce the potential for a norovirus infection and that modulation of the amount of bile acids and ceramide could potentially be used as a treatment for chronic norovirus infections that have affected people for months or years.

You can read more about the study in the paper – Bile acids and ceramide overcome the entry restriction for GII.3 human norovirus replication in human intestinal enteroids – which was recently published in the journal Proceedings of the National Academy of Sciences. DOI:  10.1073/pnas.1910138117

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