The New York Times, November 19, 2014
When we talk about viruses, usually we focus on the suffering caused by Ebola, influenza and the like. But our bodies are home to trillions of viruses, and new research hints that some of them may actually be keeping us healthy.
“Viruses have gotten a bad rap,” said Ken Cadwell, an immunologist at New York University School of Medicine. “They don’t always cause disease.”
Dr. Cadwell stumbled by accident onto the first clues about the healing power of viruses. At the time, he was studying the microbiome, the community of 100 trillion microbes living in our bodies. Scientists have long known that the microbiome is important to our health.
One of its crucial functions is ensuring that our intestines develop normally. In a healthy gut, the inner wall is lined with a dense mat of fingerlike projections called villi. When scientists raise germ-free mice in sterile cages, their intestinal villi turn out to be sparse and thin.
Germ-free mice also fail to develop a normal supply of the immune cells nestled in the lining of the gut, which attack pathogens but not harmless microbes. As a result, the germ-free mouse’s gut becomes vulnerable to injuries and infections.
In order for the gut to develop normally, an intimate chemical conversation must take place between the microbiome and host cells. Genetic mutations can disrupt this tête-à-tête, causing immune cells in the gut to attack beneficial bacteria as if they were enemies. A number of experiments suggest that ailments like inflammatory bowel disease may be the result of discord between microbes and their hosts.
Dr. Cadwell set out to understand exactly how it happens. He and his colleagues created mice with a genetic mutation known to increase the risk of inflammatory bowel disease in humans. Then the researchers examined the animals’ immune cells and guts.
In the midst of his research, Dr. Cadwell moved his mice to a new lab. And something odd happened: The move cured the mice.
Dr. Cadwell eventually figured out that the two labs differed in one important way. The old one was contaminated with a virus called murine norovirus, and the new one was virus-free.
Murine norovirus is related to the nasty human strain that causes vomiting and diarrhea — and has ruined so many cruises. The virus is harmless in healthy mice, but Dr. Cadwell found that when he gave it to his mutant mice, it triggered inflammatory bowel disease.
Dr. Cadwell was struck by how much the virus mimicked the microbiome: harmless in normal mice but triggering disease those with mutant genes. He wondered if the similarity went even further, if the virus served a purpose.
After setting up a new lab at N.Y.U. in 2011, Dr. Cadwell launched an experiment to find out. When he and his colleagues infected germ-free mice with murine norovirus, the animals developed intestines and an immune system that were fairly normal.
“It’s just one virus, but it’s doing many of the things that an entire community of bacteria is doing,” said Dr. Cadwell.
Dr. Cadwell wondered if viruses can restore the gut when it has been disturbed in other ways. Heavy doses of antibiotics, which kill off much of the microbiome, can lead to drastic changes in the gut. Some villi die, and the population of immune cells drops. But as bacteria return to the gut, the damage gets fixed.
To see whether viruses have a similar effect, Dr. Cadwell and his colleagues gave antibiotics to normal adult mice for two weeks. When they infected the mice with murine norovirus, their guts returned to normal.
Dr. Cadwell and his colleagues published the results of their experiment in Nature on Thursday.
Kristine Wylie, a research instructor of pediatrics at Washington University School of Medicine who was not involved in the research, speculated that in real life, certain viruses might be important partners with the microbiome.
“It isn’t hard to imagine that the viral exposures we get as children are important to our development,” she said.
In recent years, medical researchers have been investigating how to harness the microbiome to attack diseases. But Dr. Cadwell doesn’t expect we’ll be taking pills full of viruses to treat immune disorders. In some people, ordinarily harmless viruses might turn out to be dangerous.
Instead, Dr. Cadwell wants to figure out the molecular tricks thatthe viruses are using to improve the health of their hosts. “You’re probably going to come up with things you never imagined,” he said.
At the moment, Dr. Cadwell doesn’t know for sure how the viruses nurture the mice, but he and his colleagues have found one important clue. When they prevented germ-free mice from making a receptor on the surface of their cells, infection with norovirus didn’t lead to an improvement in their guts.
That receptor only latches onto one type of molecule. It’s called Type 1 interferon, and it’s produced by cells when they’re invaded by viruses.
Taken together, findings suggest that some viruses may be working to keep us healthy. “They did a very good job of starting to crack that nut,” said Julie K. Pfeiffer, a virologist at University of Texas Southwestern Medical Center who was not involved in the new study.
David T. Pride, a microbiologist at the University of California, San Diego, said that the new study would spur other researchers to see if they can find similar results in humans.
“The hunt for natural viruses that are beneficial to our immune systems has officially begun,” he said.
Copyright 2014 The New York Times Company. Reprinted with permission.