Researchers Find Genetic Link Between Vascular Disease and Herpes Virus

11/23/99    Portland, Ore.

For years, scientists have proposed a connection between a common herpes virus and vascular problems that occur in patients who have undergone an organ transplant or angioplasty procedure to clear clogged arteries. However, the reason behind this connection has remained a mystery. Now, researchers at Oregon Health Sciences University believe they have discovered a mechanism in the body responsible for this puzzling health problem. Their work will be published in the Nov. 24 issue of the journal Cell.

The research at OHSU centers on the human cytomegalovirus (CMV), a member of the herpes family, which has infected 50 to 85 percent of the adult population across the United States. The virus remains alive in the body for the rest of the carrier's life, but many hosts are unaware they are carriers. This is due to the fact that the virus normally remains dormant and does not cause major health problems unless a person has a suppressed immune system.

During the past 20 years, many studies have linked the virus to the development of atherosclerosis and other vascular diseases that occur in solid organ transplant recipients, or in patients who have undergone balloon angioplasty for clogged arteries.

A key part of these diseases involves the over-accumulation of smooth muscle cells in the artery wall, which can block blood flow in a vessel. CMV is often observed in these smooth muscle cells. Researchers at OHSU have uncovered evidence that a CMV gene called US28 stimulates the smooth muscle cells to migrate. Two proteins known as chemokines bind with US28 and direct the smooth muscle cells to areas of inflammation that may occur in atherosclerosis or vascular disease in transplant patients.

Dan Streblow, Ph.D., a postdoctoral fellow in microbiology and immunology at OHSU, is the principal author in the study along with co-authors Cecilia Soderberg, M.D., Ph.D., and Patsy Smith, M.S., in collaboration with Jeffery Vieira, Ph.D., at the University of Washington. Streblow calls the research a big step in understanding how viruses play a role in atherosclerosis. "It is quite rewarding to finally reveal a genetic link between CMV and vascular disease," said Streblow.

The senior author of the study, Jay Nelson, Ph.D., professor of molecular microbiology and immunology at OHSU, and director of OHSU's Vaccine and Gene Therapy Center, believes this work may provide hope for all patients at risk for vascular disease. "This work provides the smoking gun to explain the vast amount of correlative evidence linking CMV to the acceleration of vascular disease," said Nelson.

Portland-based Activated Cell Systems, L.L.C., which funded part of this project, believes that in the future this work could result in pharmaceuticals that block this process before it even starts.