CHAMPAIGN, Ill. -- Scientists studying a rotaviral strain that causes severe diarrhea in young children and neonatal pigs have isolated the virus's receptors -- where it binds -- on gastrointestinal cells and are beginning to test a synthetic mimic, which, when added to food, may block the virus.
In addition, the researchers say they may have uncovered pivotal information on activity within the virus that directs how it binds and recognizes the receptors.
"The idea is that if we can isolate and purify the receptor, which we have done, then we can add it back orally, in large amounts, in the form of a natural product that, instead of being cell bound, would be soluble," said Mark Kuhlenschmidt, professor of pathobiology in the University of Illinois College of Veterinary Medicine. "The virus would bind to this soluble receptor and pass right on through the intestinal tract and not bind to the host cell. We think this could be a viable alternative -- or an effective addition -- to a vaccine that targets the virus."
Rotavirus diarrhea is a worldwide killer of children, accounting for an estimated 870,000 deaths a year, according to the World Health Organization. While a vaccine (RRV-TV) went on the market this year, additional firepower is needed to combat the disease: The vaccine proved 92 percent effective in U.S. clinical trials, but had only a 60 percent success rate elsewhere. In animals, rotavirus-induced diarrhea kills an estimated 60 percent of its victims.
A team of U. of I. researchers reported the identification of the receptor -- a ganglioside with a simple three-sugar sequence -- in the November issue of the Journal of Virology. Co-authors of the research, which was funded by the U.S. Department of Agriculture -- were Kuhlenschmidt and his departmental colleagues Theresa B. Kuhlenschmidt, Howard B. Gelberg and former doctoral student Mark D. Rolsma, now a professor at Auburn University.
Speaking at the Second International Rushmore Conference on Mechanisms in the Pathogenesis of Enteric Diseases, Sept. 30-Oct. 3, in Rapid City, SD, Theresa Kuhlenschmidt reported preliminary, unpublished data showing the same receptor is active in humans against the Wa rotavirus -- one of four major strains that cause diarrhea in children. She also described a layered structure of the virus and suspected leptin activity that may be required for assembly of new viruses in infected cells.
"We believe this activity, which nobody has seen before, is either involved in the entry of the virus into the host intestinal cell, or in holding the virus together," Mark Kuhlenschmidt said. "All of the layers have to be present for the virus to be infective. If you remove the outer layer, it doesn't work."
The receptor is produced naturally in small amounts, he said. Cheaply produced synthetic receptors, he said, probably can be mixed into animal feed and infant formula. "Providing an oral therapy that could compete for the virus should be enough to protect from disease, but not necessarily infection," he said. "In this way, the immune system would benefit from a little bit of infection."
Journal
Journal of Virology