NIH scientists discover norovirus and other “stomach bugs” can be spread through saliva

Press release

Wednesday, June 29, 2022

A class of viruses known to cause serious diarrheal illnesses, including the one infamous for widespread outbreaks on cruise ships, can grow in the salivary glands of mice and spread through their saliva, scientists at the National Institutes of Health. The findings show that there is a new transmission route for these common viruses, which affect billions of people each year around the world and can be deadly.

Transmission of these so-called enteric viruses through saliva suggests that coughing, talking, sneezing, sharing food and utensils, and even kissing have the potential to spread viruses. The new findings still need to be confirmed in human studies.

The findings, appearing in the journal Nature, could lead to better ways to prevent, diagnose and treat diseases caused by these viruses, potentially saving lives. The study was led by the National Heart, Lung, and Blood Institute (NHLBI), part of the NIH.

Researchers have known for some time that enteric viruses, such as noroviruses and rotaviruses, can be spread by eating food or drinking liquids contaminated with fecal matter containing these viruses. Enteric viruses were thought to bypass the salivary gland and make their way to the intestines, later exiting in the feces. Although some scientists have suspected that there may be another route of transmission, this theory remained largely unproven until now.

Now researchers will need to confirm that salivary transmission of enteric viruses is possible in humans. If they find that it is, the researchers said, they may also find that this route of transmission is even more common than the conventional route. A finding like that could help explain, they said, why the large number of enteric virus infections each year around the world fails to adequately explain fecal contamination as the only route of transmission.

“This is completely new territory because these viruses were thought to only grow in the intestines,” said lead author Nihal Altan-Bonnet, Ph.D., head of the Laboratory of Host-Pathogen Dynamics at the NHLBI. “Salivary transmission of enteric viruses is another layer of transmission that we were not aware of. It’s a whole new way of thinking about how these viruses can be transmitted, how they can be diagnosed, and more importantly, how their spread can be mitigated.”

Altan-Bonnet, who has studied enteric viruses for years, said the discovery was entirely fortuitous. His team had been conducting experiments with enteric viruses in baby mice, which are the animal models of choice for studying these infections because their immature digestive and immune systems make them susceptible to infection.

For the current 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 the cages and allowed to nurse from their mothers, who were initially virus-free. After just one day, one of Altan-Bonnet’s team members, an NHLBI researcher and study co-author, Sourish Ghosh, Ph.D., noticed something unusual. The mouse pups showed an increase in IgA antibodies, important components for fighting disease, in their intestines. This was surprising considering that the mouse pups’ immune systems were immature and they were not expected to produce their own antibodies at this stage.

Ghosh also noticed other unusual things: The viruses replicated in the mothers’ breast tissue (milk duct cells) at high levels. When Ghosh collected milk from the breasts of mother mice, he found that the timing and levels of the IgA surge in the mother’s milk mirrored the timing and levels of the IgA surge in the intestines of their pups. It appeared that the infection in the mothers’ breasts had increased the production of virus-fighting IgA antibodies in their mother’s milk, ultimately helping to clear the infection in their pups, the researchers said.

Eager to learn how the viruses entered the mothers’ mammary tissue in the first place, the researchers conducted additional experiments and found that the mouse pups had not transmitted the viruses to their mothers via the conventional route, by leaving contaminated feces in a shared house. space for their mothers to eat. That’s when the researchers decided to see if the viruses in the mothers’ mammary tissue could come from the saliva of infected puppies and somehow spread during lactation.

To test the theory, Ghosh collected saliva and salivary gland samples from 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 numbers. Additional experiments quickly confirmed the salivary theory: suckling had caused viral transmission both from mother to calf and from calf to mother.

The research reported in this study was funded by the NHLBI Division of Intramural Research, part of the NIH. In addition, the research involved collaboration with two NIH National Institute of Dental and Craniofacial Research laboratories: the Biology and Utilization of Adeno-Associated Viruses for Gene Transfer (ZIA-DE000695) and the Stem/Progenitor Cell Function/ neurons during salivary gland development laboratory (ZIA-DE00722).

About the National Institutes of Health (NIH):
NIH, the nation’s medical research agency, includes 27 institutes and centers and is a component of the U.S. Department of Health and Human Services. NIH is the lead federal agency conducting and supporting basic, clinical, and translational medical research , and is researching the causes, treatments, and cures for common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

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Source: www.nih.gov