image: An enteroid ('mini-gut') was cultured in the laboratory from human intestinal precursor cells. view more
Credit: University of Pittsburgh/PNAS
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.
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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.
About the University of Pittsburgh School of Medicine
As one of the nation's leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1998. In rankings recently released by the National Science Foundation, Pitt ranked fifth among all American universities in total federal science and engineering research and development support.
Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region's economy. For more information about the School of Medicine, see http://www.medschool.pitt.edu.
Journal
Proceedings of the National Academy of Sciences