Noroviruses make people sick, but in certain mice they can help keep the gut healthy. (Three-dimensional glasses will bring this reconstruction of a norovirus into full view.)

Noroviruses make people sick, but in certain mice they can help keep the gut healthy. (Three-dimensional glasses will bring this reconstruction of a norovirus into full view.)

U. Katpally et al., J. Virol., 84, 11 (June 2010)

Viruses help keep the gut healthy

Ebola, flu, and colds have given viruses a bad rap. But there may be a good side to these tiny packages of genetic material. Researchers studying mice have shown that a virus can help maintain and restore a healthy gut in much the same way that friendly bacteria do.

The work "shows for the first time that a virus can functionally substitute for a bacterium and provide beneficial effects," says Julie Pfeiffer, a virologist at the University of Texas Southwestern Medical Center in Dallas who was not involved with the study. "It's shocking."

Our bodies are mostly microbes, with each of us hosting a hundred trillion bacteria as our so-called microbiome. These bacteria appear to play a role in everything from our weight to our allergies. But viruses also lurk in and around those bacteria—and they vastly outnumber the microbes.

Like the microbiome, this “virome” may be important for human health. One recent study, for example, found that viruses that are abundant in saliva may weed out harmful bacteria. Kenneth Cadwell, a virologist at New York University School of Medicine in New York City, wanted to know what viruses in the gut might be doing. In particular, he was interested in a group called noroviruses. Although they are notorious for causing epidemics of diarrhea on cruise ships and disease in lab mouse colonies, some noroviruses infect mice with no ill effects.

Indeed, he and his postdoc Elisabeth Kernbauer have now found that some noroviruses have a good side. In the lab, the researchers had been breeding mice in sterile environments, so the rodents and their young lack the typical portfolio of microbes and viruses that other mice have. Germ-free mice are abnormal. They don’t make enough of certain T cells, which are important for immune function, and they make too many of other immune cells implicated in allergic reactions. They also have abnormally thin villi, the microscopic fingerlike projections on the gut wall that help absorb nutrients. Other researchers had shown that giving bacteria to germ-free mice can rebalance the immune cells’ numbers and fatten the villi. Adding a norovirus to germ-free mice has the same beneficial effect, report Kernbauer, Cadwell, and Yi Ding, a pathologist at New York-Presbyterian Hospital in New York City, online today in Nature. Two other types of noroviruses similarly help make the gut healthy again, they discovered. 

In a follow-up experiment, the researchers treated normal laboratory mice with antibiotics for 2 weeks and then gave them a norovirus. The antibiotics had upset the balance of immune cells and damaged the gut lining, shrinking the villi, but as with the germ-free mice, the guts of these mice recovered with the help of the norovirus. Kernbauer and colleagues then performed the same experiment, but instead of adding the virus they replaced various bacteria knocked out by the antibiotics. Each bacterium helped restore some aspect of gut health, but not the full complement as did the virus.

In a final experiment, the team infected antibiotic-treated mice with a pathogen that causes weight loss, diarrhea, and damage to the gut wall. Treatment with the virus lessened those effects. The virus also helped protect mice against tissue damage from a toxic chemical.

Cadwell, Kernbauer, and Ding have begun to track down how the virus lends a helping hand. They found that it stimulates an immune response that involves a signaling molecule called interferon. “We have interferon as a starting point; now we want to know how interferon is conferring these benefits,” Cadwell says.

"The idea that this virus may be beneficial in some way will be hugely controversial," given that most people think of viruses in general and noroviruses in particular as harmful, says Juris Grasis, an immunologist at San Diego State University in California who was not involved with the work. Nonetheless, the study "might give us clues to human health as to what might be important in the immune system to combat or utilize noroviruses." 

The work has implications beyond noroviruses, Pfeiffer adds. Surveys of the human virome are finding lots of viruses that don't cause disease. "Maybe in some situations, they may be beneficial."