Bile Enables Norovirus to Grow in Laboratory Cell Cultures

Bile proved to be the key to the first successful growth of norovirus in laboratory cell cultures.

Noroviruses (NoVs) are a leading cause of gastroenteritis globally, yet the host factors required for NoV infection are poorly understood. Human norovirus will not infect any of the species typically used in biomedical research, such as mice, rats, or rabbits nor will it grow in human cell cultures.

After the failure of many previous attempts to cultivate norovirus in cell cultures, investigators at Baylor College of Medicine (Houston, TX, USA) turned to a recently developed human intestinal epithelial cell culture system that included enterocytes. These novel, multi-cellular human cultures, called enteroids, were made from adult intestinal stem cells from patient tissues.

The investigators reported in the August 25, 2016, online edition of the journal Science that novel cell culture system not withstanding, the method was not impressively successful until they added bile, a critical factor of the intestinal milieu. With the addition of bile, the culture system recapitulated the human intestinal epithelium, permitting human host-pathogen studies of previously non-cultivatable pathogens, and allowed the assessment of methods to prevent and treat human NoV infections.

"When we added bile to the cultures, norovirus strains that did not grow before now grew in large numbers," said senior author Dr. Mary Estes, professor of human and molecular virology and microbiology at Baylor College of Medicine. "People have been trying to grow norovirus in the lab for a very long time. We tried for the last 20 years. Despite all the attempts and the success of growing other viruses, it remained a mystery why noroviruses were so hard to work with. We were able to grow norovirus in cultures that mimic the intestinal environment, where the virus naturally grows, by adding bile to the cultures. Bile is critical for several important bacterial pathogens, but this is the first time it has been shown that bile is important for the replication of human intestinal viruses."

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