MedicalResearch.com Interview with:
Mary K. Estes, Ph.D.
Distinguished Service Professor
Cullen Endowed Chair of Human and Molecular Virology
Department of Molecular Virology and Microbiology
Baylor College of Medicine
Houston, TX 77030
MedicalResearch.com: What is the background for this study?
Response: Noroviruses are the most common cause of acute gastroenteritis (vomiting and diarrhea) worldwide and the leading cause of food-borne gastroenteritis. They also can cause chronic (long-lasting) illness in immunocompromised patients. These viruses are highly contagious and spread rapidly among people. The first report of an outbreak caused by a norovirus was in an elementary school in Norwalk, Ohio in 1968. Since that time, it became known that the virus damaged cells in the small intestine of infected people but attempts by many research groups to grow human noroviruses in the laboratory in a variety of intestinal cancer cells lines failed. This inability to grow human norovirus has been considered the single greatest barrier to norovirus research because it limited studies to understand how the virus makes people sick and how to inactivate the virus to prevent infection.
MedicalResearch.com: What are the main findings?
Response: We (the Estes lab) used a new technology to solve the 48 year mystery of noroviruses. This technology takes adult intestinal stem cells obtained from discarded patient tissues to produce “mini-gut” cultures called Human Intestinal Enteroids (HIEs) that mimic normal human intestinal cells. These cultures are able to grow several different strains of human noroviruses but only if another factor (bile), usually present in the intestine, is added to the cultures. Some strains require bile to grow while the growth of other strains is enhanced by the bile. Bile is normally released into the intestine after eating a meal to help breakdown food so this successful culture system mimics the normal intestinal environment. Also, cultures made from people with certain genetic properties are resistant to infection, similar to the resistance to infection seen in those individuals. This culture system can be used to test how to inactivate the virus in order to develop the best methods to prevent and treat future infections.
MedicalResearch.com: What should readers take away from your report?
Response: Human noroviruses infect and replicate in cells that line the intestine. An unexpected finding is that different strains of human norovirus have different growth requirements and bile either enhances or is required for virus growth. These results should bring in a new era of norovirus research. The ability to grow human noroviruses will help researchers to understand how these viruses make humans ill, develop new ways to detect the virus, evaluate methods to inactivate the virus to prevent transmission to other people, develop vaccines and drugs to prevent and treat infections, and understand whether humans develop immunity to resist repeated infections and disease.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: This study will allow people in many scientific fields to learn new information related to general virology, food and environmental virology, clinical medicine and epidemiology. Additional studies are needed to determine whether specific components of bile are required to allow or enhance human norovirus growth and how they work. Because different strains of human noroviruses grow in these novel cultures made from people with different genetic backgrounds, this system will allow us to determine if there are other human genetic and biologic factors that explain why some people get infected while others do not get infected and why the severity of illness can be different in different people.
Once inside the cell, the virus takes over the cell to replicate itself. This culture system can be used to find out how the virus does this and may lead to new ways to fight infections.
Finally, this is the first report showing these novel cultures can support the growth of a previously noncultivatable human pathogen and we predict these cultures will be useful to study other human intestinal illnesses caused by other microbes (bacteria, other viruses, parasites).
MedicalResearch.com: Is there anything else you would like to add?
Response: Our success in growing human norovirus in human intestinal cells is an example of how advances and breakthroughs in other fields of science – embryogenesis, developmental biology and stem cells – in conjunction with technological advances in tissue engineering and regenerative medicine allowed us to overcome a long-standing barrier to human norovirus research. Our ability to grow human norovirus depended on our being persistent and the development of new technology to make the novel HIEs that are not from cancer cells. This emphasizes how support for basic research in many areas is important and how new technologies resulted in our growing human norovirus.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
Replication of human noroviruses in stem cell–derived human enteroids
BY KHALIL ETTAYEBI, SUE E. CRAWFORD, KOSUKE MURAKAMI, JAMES R. BROUGHMAN, UMESH KARANDIKAR, VICTORIA R. TENGE, FREDERICK H. NEILL, SARAH E. BLUTT, XI-LEI ZENG, LIN QU,BAIJUN KOU, ANTONE R. OPEKUN, DOUGLAS BURRIN, DAVID Y. GRAHAM, SASIREKHA RAMANI,ROBERT L. ATMAR, MARY K. ESTES
PUBLISHED ONLINE25 AUG 2016
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