Besides their chubby cheeks and cute little toes, I think what makes newborns so precious is how vulnerable they are in those first few days and months of life. For instance, infants are particularly easy targets for infections of the gut caused by enteroviruses. While healthy adults infected with these viruses may exhibit mild cold or flu-like symptoms, infants can have serious complications including sudden onset paralysis, infection of the heart and brain, even death.
Not much is known about how these viruses enter the gut and gain entry to other parts of the body. Reporting this week in PNAS, a research team at the Washington University School of Medicine in St. Louis used human stem cell-derived “mini-guts” to uncover some clues.
The intestine is a very complex organ with several different cell types that work in concert to keep bacteria and viruses out, and to allow food to be absorbed into the bloodstream. This complexity has made it difficult to carry out human studies in the lab that adequately mimic enterovirus infection. To overcome these challenges, the team isolated stem cells from the small intestine of a premature infant and successfully generated mini-intestines in petri dishes.
The researchers then tested the ability of various enteroviruses to infect the mini-guts and observed they were most vulnerable to infection by enterovirus E11, the most common enterovirus infection seen in premature infants. The team went on to show that the E11 virus infects some cell types of the mini-gut but not others.
In a press release, Co-senior author Carolyn Coyne, an associate professor at the University of Pittsburgh School of Medicine, described the importance of this work for the 10 to 15 million enterovirus infections and tens of thousands of hospitalizations each year in the U.S.:
“Despite their major global impact, especially on the health of children, little is known about the route that these viruses take to cross the intestine, their primary point of entry. Our approach has for the first time shed some light on this process. This model also could be used for developing anti-enterovirus therapeutics targeting the gastrointestinal tract, given that no therapeutic approaches exist to combat infections of these viruses.”