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Scripps research team sheds light on immune system suppression
Date:10/17/2008

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When plasmacytoid dendritic cells come in contact with viruses and other foreign invaders, they bind with them via membrane proteins known as toll-like receptors. Under normal conditions, this binding triggers massive production of type I interferon that then triggers other immune responses.

But the lymphocytic choriomeningits virus, and presumably other immunosupressor viruses like measles and HIV, disable this system. This then compromises other reactions, most critically activation of the natural killers that would otherwise destroy the virus-infected cells, as well as other invaders.

The researchers showed that once in this infected condition, a secondary opportunistic agent, in this case the herpes virus murine cytomegalovirus, which the mice could have otherwise fought off, grew unchecked. Remarkably, opportunistic infections with herpes viruses are frequently observed in patients infected with HIV and the mechanism described in this study could well be one of the underlying causes.

One critical aspect of the group's findings is that while the initial lymphotcytic choriomeningitis virus effectively blocked interferon production, it did not kill the dendritic cells, instead allowing them to function as long-term hosts. This allows such viruses to persist, causing persistent immunosuppression.

"I think the implications are that many of the diseases we don't know the causes for, be they behavioral, mental, cardiovascular, or endocrine, may well be caused by viruses that persist without destroying the differentiated cells they infect, alter their functions, and by this means alter homeostasis and cause disease," says Oldstone. "Examples would be viruses that persistently infect neurons and cause problems in learning and behavior, viruses that infect oligodendrocytes and cause demyelination, and viruses that infect endocrine cells and alter their production of hormones. There may be some differences, but most ce
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Contact: Keith McKeown
kmckeown@scripps.edu
858-784-8134
Scripps Research Institute
Source:Eurekalert

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