Contact: Daniel Sedmak, (614) 292-4692
Written by Darrell E. Ward, (614) 292-8456
RESEARCHERS UNCOVER NEW VIRAL DEFENSE MECHANISM
COLUMBUS, Ohio -- Researchers have uncovered one method by which a common virus that can cause serious illness and death in immune-suppressed patients is able to evade the body's defenses.
The virus is cytomegalovirus (CMV). Forty to 60 percent of Americans are thought to carry the virus, which ordinarily doesn't cause health problems in people who have a healthy immune system.
But CMV is a leading cause of death in bone marrow transplant patients and may lead to pneumonia and other serious problems in cancer patients and transplant recipients. In AIDS patients, CMV causes blindness and a variety of devastating illnesses. In addition, it can cause mental retardation and other problems in children born to women who become CMV-infected for the first time during pregnancy.
Researchers found that CMV tricks an infected cell into destroying a key protein used to alert cells that an infecting virus is present.
"We've discovered yet another way in which CMV avoids detection by the immune system," said Daniel Sedmak, professor and chair of pathology and a researcher with Ohio State University's Comprehensive Cancer Center.
"The virus has evolved a clever means of disabling a major protective process in the cell."
The findings, reported in a recent issue of the Journal of Experimental Medicine, could lead to treatments that allow the immune system to eliminate CMV before it becomes a problem in immune-suppressed patients.
Furthermore, the findings might provide a new strategy for turning off unwanted immune responses, such as those that occur during autoimmune disease or graft rejection.
"CMV is an ancient virus that has co-evolved with the human immune system," said Sedmak. "It has succeeded in living in such a way that it doesn't destroy its host, while at the same time developing the means to avoid being destroyed by its host."
"But in people with weakened or suppressed immunity, the immune system can no longer control the virus, and it causes disease."
Normally, cells reveal the presence of an infecting virus by displaying bits of the virus on the cell surface. There, immune-system cells can detect the foreign material and inititate an immune reaction against the virus. That immune response would destroy the cell and the infecting viruses along with it.
A key player in this protective mechanism is a protein known as Janus kinase 1, or Jak1. Jak1 is also the protein CMV has learned to knock out in infected cells.
Unfortunately for the cell -- but fortunately for the virus -- Jak1 plays a role in several anti-viral immune-response pathways.
By eliminating Jak1, CMV derails these defense mechanisms and the immune responses that would otherwise work to eliminate it. This enables some infecting viruses to avoid immune detection and maintain a long-term, low-level infection of the body.
That is, until a medical procedure or disease weakens the immune system and allows CMV to cause disease.
Sedmak and his research team are now working to identify the CMV protein that initiates the destruction of Jak1.
Sedmak's study was funded by a grant from the National Institutes of Health. Daniel Miller, a medical sciences student in Sedmak's laboratory, led the study.
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