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An enteroid (‘mini-gut’) cultured in the laboratory from human intestinal precursor cells

Credit: University of Pittsburgh/PNAS  

 (Click for high-res image)
 
A normal ‘mini-gut’ cultured in a dish (left) and one damaged by enterovirus E11 infection (right)
 
Credit: University of Pittsburgh/PNAS
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Inside Passage: Researchers Shed Light on How Viruses Enter the Intestine

PITTSBURGH, Jan. 30, 2017 – Researchers at the University of Pittsburgh and Washington University in St. Louis have provided the first details of how enteroviruses, which cause millions of infections worldwide annually, may enter the body through the intestine. The results of the study are published this week in the journal Proceedings of the National Academy of Sciences.
 
Enteroviruses are a class of viruses that are the second most common human infectious agents and are primarily transmitted through close person-to-person contact, touching infected surfaces, or ingesting food or water containing the virus.
 
Enterovirus infections are associated with diseases that can range from mild flu-like symptoms to much more severe outcomes such as inflammation in the brain or heart, acute paralysis, and even death. Enterovirus infections acquired within neonatal intensive care units (NICU) can be devastating as newborns are particularly susceptible to infection by these viruses.
 
“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,” said senior author Carolyn Coyne, Ph.D., associate professor of microbiology and molecular genetics at the Pitt School of Medicine.
 
In the study, researchers isolated stem cells from premature human small intestines and grew them in the laboratory into enteroids, or so-called “mini-guts,” which contained the different cell types and tissue structures that are normally found in the human intestine.
 
Using the mini-gut model, they demonstrated that echovirus 11 (E11), the enterovirus most commonly associated with NICU infections, induced significant damage to the enteroids, which could facilitate passage of the virus into the bloodstream from the infected intestine.
 
The results also provided the first evidence that different types of enteroviruses could target distinct cells within the gastrointestinal tract and might vary in their effectiveness at infecting intestinal cells.
 
“This study not only provides important insights into enterovirus infections, but also provides an important model that could be used to test the efficacy of anti-enterovirus therapeutics in the premature intestine,” said Misty Good, M.D., assistant professor of pediatrics at the Washington University School of Medicine in St. Louis and co-senior author of the study.
 
Other authors of the study included Coyne G. Drummond, B.S., and Congrong Ma, M.Sc., of the University of Pittsburgh; and Alexa M. Bolock, B.S., and Cliff J. Luke, Ph.D., of Washington University School of Medicine in St. Louis.
 
The study was funded by National Institutes of Health grants R01AI081759 and K08DK101608, the Burroughs Wellcome Fund, and Children’s Hospital of Pittsburgh of UPMC.

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