July 11, 1996
Media Contact: Marc Kusintz
Phone: (410) 955-8665
Johns Hopkins researchers have discovered an important way by which the measles virus weakens the immune system, leaving infected individuals in developing countries more vulnerable to deadly infections. The finding helps to explain why measles is a major cause of death in those areas, and also may help to explain how the AIDS virus weakens the immune system.
Working with laboratory cell cultures, the Hopkins researchers showed that the measles virus blocks the release of an important chemical from monocytes, a type of white blood cell. The molecule, called Interleukin-12, or IL-12, is critical for the activation of a part of the immune system called cell-mediated immunity (CMI). CMI is an important defense mechanism against a variety of viruses, bacteria, as well as protozoa, one type of which causes malaria. In the absence of IL-12 production by monocytes, CMI is greatly weakened. The study was funded in part by the National Institutes of Health.
"Our study may explain why measles is so dangerous in places where the disease is widespread and medical care is limited," says Christopher Karp, M.D., assistant professor of medicine and lead author of a report on the findings, published in the July 12 issue of Science. "In the developing world, up to two million children die each year from diseases like pneumonia and diarrhea after they get measles."
The results also may explain the finding by other researchers that live, weakened measles virus vaccines also have been found in laboratory studies to cause similar effects in the CMI. Karp emphasizes, however, that the current measles vaccine used in the United States is both safe and effective.
Karp's team showed that the measles virus needn't get inside monocytes to suppress immunity; the virus only had to bind to certain molecules on the cell's surface. The virus forms a bridge between these molecules, called CD46 proteins. When these proteins become linked, the cell stops releasing IL-12.
The Hopkins team also found that a group of immune system substances called complement proteins turns off IL12 release from monocytes. Complement proteins can apparently also link CD46 molecules together, preventing monocytes from releasing IL-12, according to Karp. The ability of complement to shut down production of IL-12 by measles also may be part of the process by which the AIDS virus suppresses the immune system, he adds.
In order to see how closely his laboratory results reflect what's happening in children, Karp next plans to study the levels of IL-12 in the blood of children with measles in developing countries.
The type of measles virus studied by the Hopkins team is the common, childhood, rubeola measles.
Other authors of the study include Joseph M. Ahearn, M.D., Ph.D., Peter J. Cuomo, B.A., and Diane Griffin, M.D., Ph.D. (Johns Hopkins); Maria Wysocka, Ph.D., and Giorgio Trinchieri, M.D. (Wistar Institute of Anatomy and Biology, Philadelphia); Larry M. Wahl, Ph.D. (National Institute of Dental Research, NIH); and Barbara Sherry, Ph.D. (Picower Institute for Medical Research, Manhasset, N.Y.).
Additional funding for the study was provided by the Peggy Meyerhoff Pearlstone Foundation and the World Health Organization.