Measles virus reveals its killing ways.
Scientists now report that they have finally discovered a crucial detail of how the measles virus exacts its deadly toll.
Investigators have long known that, like the AIDS virus, the measles virus kills indirectly, weakening an infected person's immune system so that he or she becomes more susceptible to other pathogens. It's those secondary infectious agents, which may cause pneumonia, diarrhea, or other diseases, that can prove fatal, especially in countries with poor medical care. The measles virus appears to make people vulnerable to other infections by preventing immune cells called monocytes and macrophages from manufacturing a molecule vital to a strong cellular immune response, report Christopher L. Karp of the Johns Hopkins Medical Institutions in Baltimore and his colleagues in the July 12 Science.
The researchers had initially focused their attention on other immune cells called lymphocytes. While the ability of these cells to proliferate and react to infection was clearly diminished in measles patients, the investigators found that the measles virus did not concentrate its attack on the cells. "The lymphocytes were being affected, but they were not infected," says Diane E. Griffin, a report coauthor also from Johns Hopkins.
Griffin and her colleagues found that the measles virus incapacitates lymphocytes by attacking monocytes and macrophages. These immune cells have a number of roles, such as producing interleukin-12 (IL-12), a molecule needed to trigger a strong lymphocyte response.
The investigators discovered that the measles virus dramatically decreases the amount of IL-12 made by monocytes and macrophages. The virus "doesn't even have to infect the cells. All it has to do is interact with their measles receptor. That shuts down the ability of those cells to make IL-12," says Griffin.
The measles receptor is a cell surface protein called CD46. Apart from inadvertently allowing the measles virus access to cells, CD46's best-known function is to snare a few of the immune system proteins known collectively as complement. The complete complement system forms complexes that attach to and kill bacteria and other pathogens. CD46 prevents similar attacks on the body's own cells by not allowing the complement proteins to form these complexes. The new research, says Griffin, indicates that CD46 responds to the measles virus by sending signals into the interior of the immune cell, including one that prompts it to reduce IL-12 production.
Griffin notes that she and her colleagues have shown only that the measles virus lessens IL-12 output in laboratory-grown monocytes and macrophages. To confirm that this phenomenon takes place during an actual measles infection, the investigators need to examine the immune cells of infected people. "We're looking for a large measles outbreak," says Griffin. The investigators are trying to set up monitoring programs in Zimbabwe and Zaire, for example. Administering IL-12 to people with measles may offer one option for preventing secondary infections, acknowledges Griffin. But, she warns, IL-12 is a powerful drug that can produce severe side effects, including death, if injected throughout the body (SN: 6/17/95, p. 375). A safer option for measles patients, says Griffin, might be to develop a drug that prevents CD46 from telling cells to stop making IL-12.
Investigators are also curious as to whether other viruses weaken the immune system by using CD46. Karp suggests that part of the immunosuppression seen in AIDS patients, including the diminished capacity of immune cells to make IL-12, may result from the tweaking of CD46 by complement proteins bound to the AIDS virus. "There's a lot of tantalizing hints but no direct data yet," he says.
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|Title Annotation:||virus disrupts immune response|
|Date:||Jul 13, 1996|
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