Stomach bugs sweep through schools and workplaces every year around the world. Norovirus is often the culprit. In the United States, this infection tends to strike from November to April. Family members can fall ill one after another. Whole schools can shut down because so many kids and teachers are out sick. It’s a very contagious disease that causes vomiting and diarrhea. Now, scientists have learned just how this nasty virus takes over the gut. New data in mice show that it homes in on one rare type of cell.
Norovirus is actually a family of viruses. One of its members emerged at the 2018 Winter Olympics in Pyeongchang, South Korea. There, it sickened 275 people, including some of the athletes. Globally, noroviruses cause about 1 in 5 cases of gut-wrenching stomach illness. In countries where healthcare is good and easy to get, it’s mostly inconvenient. The viruses keep their victims home from work and school. But in countries where healthcare is more costly or hard to get, norovirus infections can prove lethal. Indeed, each year more than 200,000 people die from them.
Scientists had not known much about how these viruses do their dirty work. They didn’t even know what cells the viruses targeted. Until now.
Craig Wilen is a physician scientist at the Washington University School of Medicine in St. Louis, Mo. Previously, his team had shown in mouse studies that to enter cells, noroviruses need a specific protein — molecules that are important parts of all living things. They used that protein to home in on the viruses’ target.
That key protein showed up on only one rare type of cell. It lives in the lining of the intestine. These cells stick tiny finger-like projections into the gut wall. This cluster of tiny tubes sticking off the ends of the cells looks like a “tuft.” That explains why these are known as tuft cells.
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Tuft cells seemed like the prime targets for norovirus because they had the gate-keeper protein needed to let the virus in. Still, the scientists needed to confirm the cells’ role. So they tagged a protein on the norovirus. That tag caused the cell to light up when the virus was inside it. And sure enough, like beacons in a dark sea, tuft cells glowed when a mouse developed a norovirus infection.
If noroviruses also target tuft cells in people, “maybe that’s the cell type we need to be treating” to stop the illness, says Wilen.
He and his colleagues shared their new findings April 13 in the journal Science.
Tuft cells in tough guts
Identifying a role for tuft cells in a norovirus attack “is a significant step forward,” says David Artis. He is an immunologist — someone who studies how organisms ward off infections — at Weill Cornell Medicine in New York City. He was not involved in the study.
Scientists had already linked tuft cells in 2016 to one immune response. These cells turned on when they sensed the presence of parasitic worms. Those worms can live in the gut, feasting off the food flowing by. When tuft cells notice these intruders, they produce a chemical signal. It warns nearby tuft cells to multiply, creating legions big enough to fight off the parasite.
Research had also shown that the presence of parasites makes a norovirus infection worse. Perhaps the extra tuft cells that arise during a parasite infection are part of the reason. Uh oh. Wilen says these extra tuft cells seem to be “good for the virus.”
Finding out how norovirus tackles tuft cells may be important for more than just preventing a short-lived bout of vomiting and diarrhea. It might also help researchers who want to understand inflammatory bowel diseases. These chronic conditions inflame the gut — often for decades. This can cause intense pain, diarrhea and more.
Researchers now speculate that some outside trigger — like a norovirus infection — might be what ultimately turns on these digestive diseases. In one 2010 study, Wilen notes, mice with genes that make the rodents especially likely to develop an inflammatory bowel disease showed symptoms of that disease after being infected with norovirus.
The finding that norovirus infects tuft cells was “shocking,” Wilen says. This information could motivate a lot more research.
Norovirus is good at making many, many copies of itself during an infection. To do that, they must first hijack the copying “machinery” of the cells they infect. Norovirus will only hijack a tiny share of tuft cells. Studying why could help scientists better understand this scourge — and each year spare many people a lot of misery.
bug The slang term for an insect. Sometimes it’s even used to refer to a germ.
cell The smallest structural and functional unit of an organism. Typically too small to see with the unaided eye, it consists of a watery fluid surrounded by a membrane or wall.
chemical A substance formed from two or more atoms that unite (bond) in a fixed proportion and structure. For example, water is a chemical made when two hydrogen atoms bond to one oxygen atom. Its chemical formula is H2O. Chemical also can be an adjective to describe properties of materials that are the result of various reactions between different compounds.
colleague Someone who works with another; a co-worker or team member.
contagious An adjective for some disease that can be spread by direct contact with an infected individual or the germs that they shed into the air, their clothes or their environment. Such diseases are referred to as contagious.
diarrhea (adj. diarrheal) Loose, watery stool (feces) that can be a symptom of many types of microbial infections affecting the gut.
gut An informal term for the gastrointestinal tract, especially the intestines.
immune (adj.) Having to do with the immunity. (v.) Able to ward off a particular infection. Alternatively, this term can be used to mean an organism shows no impacts from exposure to a particular poison or process. More generally, the term may signal that something cannot be hurt by a particular drug, disease or chemical.
infection A disease that can spread from one organism to another. It’s usually caused by some type of germ.
inflammatory bowel disease (IBD) A term for several potentially severe conditions that regularly (chronically) inflame the digestive tract. The two most common types of this disease are ulcerative colitis (which inflames the large intestine, or colon) and Crohn’s disease (which inflames the entire digestive tract). Both conditions stem from the immune system's abnormal response to the affected tissues. That means they are autoimmune diseases. Symptoms can include diarrhea, blood in the stool, abdominal pain and extreme fatigue.
journal (in science) A publication in which scientists share their research findings with experts (and sometimes even the public). Some journals publish papers from all fields of science, technology, engineering and math, while others are specific to a single subject. The best journals are peer-reviewed: They send all submitted articles to outside experts to be read and critiqued. The goal, here, is to prevent the publication of mistakes, fraud or sloppy work.
molecule An electrically neutral group of atoms that represents the smallest possible amount of a chemical compound. Molecules can be made of single types of atoms or of different types. For example, the oxygen in the air is made of two oxygen atoms (O2), but water is made of two hydrogen atoms and one oxygen atom (H2O).
organism Any living thing, from elephants and plants to bacteria and other types of single-celled life.
parasite An organism that gets benefits from another species, called a host, but doesn’t provide that host any benefits. Classic examples of parasites include ticks, fleas and tapeworms.
protein A compound made from one or more long chains of amino acids. Proteins are an essential part of all living organisms. They form the basis of living cells, muscle and tissues; they also do the work inside of cells. Among the better-known, stand-alone proteins are the hemoglobin (in blood) and the antibodies (also in blood) that attempt to fight infections. Medicines frequently work by latching onto proteins.
symptom A physical or mental indicator generally regarded to be characteristic of a disease. Sometimes a single symptom — especially a general one, such as fever or pain — can be a sign of any of many different types of injury or disease.
tuft cell These are rare cells that live in the lining of the intestine and in places like the lungs and trachea. These cells sense chemicals by projecting tiny fingers into the intestine and lungs. Bunches of these fingers look like little tufts, giving the tuft cell its name.
virus Tiny infectious particles consisting of RNA or DNA surrounded by protein. Viruses can reproduce only by injecting their genetic material into the cells of living creatures. Although scientists frequently refer to viruses as live or dead, in fact no virus is truly alive. It doesn’t eat like animals do, or make its own food the way plants do. It must hijack the cellular machinery of a living cell in order to survive.
Journal: 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.
Journal: M Howitt et al. Tuft cells, taste-chemosensory cells, orchestrate parasite type 2 immunity in the gut. Science. Vol. 351, March 18, 2016, p. 1329. doi: 10.1126/science.aaf1648.
Journal: Cadwell et al. Virus-plus-susceptibility gene interaction determines Crohn's disease gene Atg16L1 phenotypes in intestine . Cell. Vol. 141, June 25, 2010, p. 1135. doi: 10.1016/j.cell.2010.05.009.