The pathogen targets a rare type of gut cell, a study in mice finds
C. Wilen et al/Science 2018
How a nasty, contagious stomach virus lays claim to the digestive system just got a little less mysterious.
In mice, norovirus infects rare cells in the lining of the gut called tuft cells. Like beacons in a dark sea, these cells glowed with evidence of a norovirus infection in fluorescent microscopy images, researchers report in the April 13 Science.
If norovirus also targets tuft cells in humans, “maybe that’s the cell type we need to be treating,” says study coauthor Craig Wilen, a physician scientist at the Washington University School of Medicine in St. Louis.
Worldwide, norovirus causes about 1 in 5 cases of acute gastroenteritis, an illness of vomiting and diarrhea accompanied by rapid dehydration. More than 200,000 people die annually from the virus, nearly all in developing countries. Norovirus even popped up at the 2018 Winter Olympics in Pyeongchang, South Korea, reportedly infecting around 275 people including a few competing athletes.
But little is known about how norovirus, which is actually a group of viruses, does its dirty work in the body — including what cells it targets. Identifying a role for tuft cells in the interactions between the virus and its host “is a significant step forward,” says immunologist David Artis of Weill Cornell Medicine in New York City, who was not involved in the study.
Wilen and colleagues had previously discovered the protein that norovirus requires to enter cells in mice. They used that clue to uncover the role of the tuft cells, which have recently been tied to a certain type of immune response. The cells get their name from a cluster of tube structures sticking off of one end.
The finding that norovirus targets tuft cells fits with previous research on the virus and other pathogens. Intestinal parasitic worms can make a norovirus infection worse in mice. And tuft cells are known to increase in number during these parasite infections.
Killing off gut bacteria has also stopped norovirus infections in mice. In the new study, Wilen and colleagues found that knocking out the bacteria with antibiotics decreased the genetic activity of tuft cells. Having more tuft cells seems to be “good for the virus,” Wilen says.
The tuft cells-norovirus connection may prove fruitful for research into inflammatory bowel disease as well. There are certain forms of genes that slightly increase the risk of developing Crohn’s disease or ulcerative colitis. Researchers speculate that an outside trigger such as an infection might be what ultimately unleashes these diseases. In another study, Wilen notes, mice genetically predisposed to have Crohn’s disease developed symptoms of that disease after being infected with norovirus.
C. Wilen et al. Tropism for tuft cells determines immune promotion of norovirus pathogenesis. Science. Vol. 360, April 13, 2018, p. 204. doi:10.1126/science.aar3799.