June 23, 2008
UI team helps discover how measles virus spreads within a body
Measles, one of the most common contagious diseases, has been thought to enter the body through the surface of airways and lungs, like many other major viruses. Now, Mayo Clinic researchers and collaborators, including two at the University of Iowa, say that is not the case, and some medical texts will need to be revised.
The findings, which have implications for disease treatments, are reported in the June 20 online edition of the Journal of Clinical Investigation (www.jci.org). The study was led by Roberto Cattaneo, Ph.D., virologist at Mayo Clinic, and involved UI researchers Paul McCray, M.D., and Patrick Sinn, Ph.D., who provided the study a model system that closely mimics the cells lining the human airways.
"It has long been assumed that measles virus infects the airway epithelium before infecting immune cells," Cattaneo said. "But we've shown that replication in the airways is not required, and that a virus replicating only in immune cells causes measles in monkeys."
The research team generated a measles virus that cannot enter the airway epithelium and showed in rhesus monkeys that it spread in lymphocytes (immune system cells) and remained virulent. The monkeys developed rashes and lost weight, which are typical measles symptoms in the species. Follow-up tests showed the virus could not cross the respiratory epithelium on its way out of the lungs and was not shed from the infected monkeys, although the lymph system was infected.
The researchers said that from a treatment standpoint, the findings help physician-researchers better understand how the measles virus, which can be reprogrammed to eliminate cancer cells, spreads in hosts.
"The research may help lead to more effective and safe cancer therapies. It also could help us understand how viruses similar to measles function and help with the development of more effective vaccines for other diseases," said McCray, professor of pediatrics at the UI Roy J. and Lucille A. Carver College of Medicine and a pediatrician with UI Children's Hospital.
"What the UI helped show, in particular, is that measles virus binds to a receptor and enters through the bottom of respiratory cells, not the top, as previously thought," said Sinn, associate research scientist in pediatrics at the UI Carver College of Medicine.
The bottom surface of the cells faces tissues, whereas the top surface faces the airways. The specific receptor, a protein that the measles virus particles bind to on respiratory epithelial cells, has yet to be identified. "Identifying that protein would be a key step towards the development of new treatments," Sinn said.
From a strictly scientific perspective, the study challenges a widely held assumption about measles. The researchers cite two recent medical texts on the measles virus that say it infects the upper respiratory epithelium before spreading to the rest of the body. In light of their findings, the investigators say those statements will have to be revised.
"It was a very productive collaboration. Each team brought expertise to a study that none of us could have done alone," Sinn said.
Additional co-authors on the paper include Vincent Leonard, Ph.D., Tanner Miest, and Patricia Devaux, Ph.D., Mayo Clinic; Gregory Hodge and Michael B. McChesney, Ph.D., University of California Davis; Numan Oezguen, Ph.D., and Werner Braun, Ph.D., University of Texas Medical Branch, Galveston.
Support for the study came from the National Institutes of Health and from a grant from the Roy J. Carver Charitable Trust to McCray.
NOTE TO EDITORS: This news release includes information used with permission from a Mayo Clinic embargoed news release.
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