Researchers have for the first time grown a human norovirus in a cell culture dish, taking a step toward developing medications to treat the stomach bug that strikes millions of people every year in schools, hotels, and cruise ships.
Says Stephanie Karst, associate professor in the molecular genetics and microbiology department at University of Florida College of Medicine:
“The biggest hurdle to doing norovirus research for its entire history—since it was discovered in 1972—has been that we can’t culture the human viruses in a cell culture dish.
That complicates every aspect of research. We can’t study how it replicates, we can’t test therapeutics, and we can’t generate live virus vaccines.”
Noroviruses are intestinal viruses that cause violent vomiting and diarrhea. People ill with the virus remain contagious up to three days after they seem to recover.
Although a vaccine for these viruses is in clinical trials, there is still no medication to combat them. That’s in part because researchers have not been able to culture human noroviruses so they can test potential treatments.
Tough Virus To Beat
In the United States alone, human noroviruses cause 19 million to 21 million cases of illness every year, and contribute to 56,000 to 71,000 hospitalizations and 570 to 800 deaths, mostly in young children and older adults.
They are resistant to many common disinfectants, and very little of the virus is needed to infect a host, so a surface may still contain enough virus to infect a person even after it is cleaned.
Previous research has speculated that noroviruses primarily target intestinal epithelial cells, which line the intestine and protect it from pathogens. But the new study demonstrates that the virus targets B cells, a type of white blood cell common in the intestine.
“That’s a big surprise,” Karst says. “You would think that any virus that’s going to target the intestine would instead target the intestinal epithelial cells because that’s the first cell the virus is going to encounter.”
Researchers were also surprised to find that bacteria present in the body’s gut flora, also known as commensal bacteria, helped the human norovirus infect B cells. Scientists have long known that noroviruses need a particular kind of carbohydrate to infect cells.
“What we’ve shown is that noroviruses attach to that carbohydrate expressed on commensal bacteria, and that this interaction stimulates viral infection of the B cell,” Karst says.
“This is a really exciting, emerging theme. A variety of intestinal viruses seem to exploit the bacteria that are present in our intestines all the time. These viral infections are enhanced by the presence of bacteria in the gut.
Ultimately, this system should open up new avenues for norovirus vaccine and antiviral drug development.”
Melissa K. Jones, Makiko Watanabe, Shu Zhu, Christina L. Graves, Lisa R. Keyes, Katrina R. Grau, Mariam B. Gonzalez-Hernandez, Nicole M. Iovine, Christiane E. Wobus, Jan Vinjé, Scott A. Tibbetts, Shannon M. Wallet, and Stephanie M. Karst Enteric bacteria promote human and mouse norovirus infection of B cells Science 7 November 2014: 346 (6210), 755-759. DOI:10.1126/science.1257147
Illustration: Norwalk virus capsid Norovirus. Credit: Anna Tanczos. Wellcome Images