Researchers with the National Institutes of Health have found that a class of viruses known to cause severe diarrheal diseases can grow in the salivary glands of mice and spread through their saliva.
Although the findings need to be confirmed in human studies, they suggest a new route of transmission for enteric viruses like noroviruses and rotaviruses, which infect billions annually and can be fatal. Published recently in Nature, the study could also lead to better ways to prevent, diagnose, and treat such viruses.
Researchers have known for some time that enteric viruses, such as noroviruses and rotaviruses, can spread by eating food or drinking liquids contaminated with fecal matter containing these viruses. Enteric viruses were thought to bypass the salivary gland and target the intestines, exiting later through feces. Although some scientists have suspected there may be another route of transmission, this theory remained largely untested until now.
“This is completely new territory because these viruses were thought to only grow in the intestines,” says senior author Nihal Altan-Bonnet, Ph.D., chief of the Laboratory of Host-Pathogen Dynamics at NIH’s National Heart, Lung, and Blood Institute (NHLBI). “Salivary transmission of enteric viruses is another layer of transmission we didn’t know about. It is an entirely new way of thinking about how these viruses can transmit, how they can be diagnosed, and, most importantly, how their spread might be mitigated.”
Altan-Bonnet, who has studied enteric viruses for years, said the discovery was completely serendipitous. Her team had been conducting experiments with enteric viruses in infant mice, which are the animal models of choice for studying these infections because their immature digestive and immune systems make them susceptible to infections.
For the study, the researchers fed a group of newborn mice that were less than 10 days old with either norovirus or rotavirus. The mouse pups were then returned to cages and allowed to suckle their mothers, who were initially virus-free. After just a day, one of Altan-Bonnet’s team members, NHLBI researcher and study co-author Sourish Ghosh, Ph.D., noticed something unusual: the mouse pups showed a surge in IgA antibodies—important disease-fighting components—in their guts. This was surprising considering that the immune systems of the mouse pups were immature and not expected to make their own antibodies at this stage.
Ghosh also noticed that the viruses were replicating in the mothers’ breast tissue at high levels. When Ghosh collected milk from the breasts of the mouse mothers, he found that the timing and levels of the IgA surge in the mothers’ milk mirrored the timing and levels of the IgA surge in the guts of their pups. It seemed the infection in the mothers’ breasts had boosted the production of virus-fighting IgA antibodies in their breast milk, which ultimately helped clear the infection in their pups.
Eager to know how the viruses got into the mothers’ breast tissue in the first place, the researchers conducted additional experiments and found that the mouse pups had not transmitted the viruses to their mothers by leaving contaminated feces in a shared living space for their mothers to ingest. That’s when the researchers decided to see whether the viruses in the mothers’ breast tissue might have come from the saliva of the infected pups and somehow spread during breastfeeding.
To test the theory, Ghosh collected saliva samples and salivary glands from the mouse pups and found that the salivary glands were replicating these viruses at very high levels and shedding the viruses into the saliva in large amounts. Additional experiments quickly confirmed the salivary theory: Suckling had caused both mother-to-pup and pup-to-mother viral transmission.
The findings help explain why the high number of enteric virus infections each year worldwide fails to adequately account for fecal contamination as the sole transmission route. The work also has implications for therapeutics, diagnostics and sanitation measures aimed at preventing spread through saliva.