Mar. 5, 1998 by Chris Woolston
Most people know that cigarettes and high-fat food can contribute to atherosclerosis, the leading killer in the developed world. But is an unhealthy lifestyle all it takes to clog arteries? A small but vocal group of researchers believes atherosclerosis starts with a virus, not a cheeseburger. According to the theory, vascular damage caused by a virus could lay a foundation for the build-up of plaque.
Though it has its supporters, this theory has always suffered a credibility problem -- there has never been any direct evidence that viruses can injure human vessels. Now, thanks to a surprising discovery at Washington University School of Medicine in St. Louis, there is a new reason to reconsider the idea. In a recent issue of Nature Medicine, the researchers reported that a virus related to those that cause mononucleosis and Kaposi's sarcoma can injure arteries in mice, the first time such an effect had been seen in mammals. The study was supported by Monsanto-Searle, the National Institutes of Health and the National Cancer Institute.
"We're still a long way from showing that viruses can trigger atherosclerosis or other vascular diseases in humans," says senior author Herbert W. Virgin, M.D., Ph.D., an assistant professor of pathology, molecular microbiology and medicine. "But now we have a better idea that it may be possible, and we know which viruses might be involved."
The discovery at the School of Medicine echoes recent studies that suggest a link between bacterial infections and some vascular diseases. That link is still inconclusive, but Virgin believes it's entirely possible that both viruses and bacteria might be capable of damaging blood vessels and triggering disease. "It's highly unlikely that one single agent is the cause of all vascular disease," he says.
If viruses do in fact set the stage for atherosclerosis, physicians may someday be able to prevent the disease with a vaccine, Virgin says. But even if that's theoretically possible, such a vaccine lies far in the future, he adds. For now, viruses may be unavoidable, but people can still prevent atherosclerosis by staying away from high-fat food and cigarettes, Virgin explains. "At most, viruses could initiate only the earliest stages of the disease," he says. "They certainly couldn't block arteries on their own."
Damage resembles human diseases
Normal mice never develop full-blown atherosclerosis, which makes them imperfect models, Virgin says. Nevertheless, he and his colleagues found lesions that somewhat resembled the early stages of the disease. As with atherosclerosis, the damage was limited to the major arteries. Most importantly, the injured portions began to accumulate fatty plaque.
The vascular injuries also closely mimicked a group of human vascular diseases -- Taskayasu's arteritis, temporal arteritis and Kawasaki's disease -- whose origins have always been a mystery. The early stages of these diseases are marked by rashes and fever, symptoms typical of viral infection. "If it turns out that viruses cause these diseases in humans, few physicians would be surprised," says co-researcher Samuel H. Speck, Ph.D., an associate professor of pathology and molecular microbiology. "The link between viruses and atherosclerosis is much more controversial."
Intriguingly, infections in newborn mice led to fatal vascular disease when the animals were well into adulthood. "The infection doesn't cause vascular disease immediately, but it seems to set the whole process in motion," Virgin says. "This may suggest a model for how atherosclerosis and other vascular diseases progress in humans." The virus had little effect on healthy adult mice but did cause severe vascular disease in adult mice with compromised immune systems. At first, Virgin, Speck and colleagues had no intention of studying vascular disease; they fully expected the mouse virus to cause cancer. "The virus had been associated with lymphoma, but nobody had any idea it could damage arteries," Speck says. "When we dissected infected mice and saw the damage, we were quite surprised."
Viruses under suspicion
The virus used in the study is found only in mice, but it's closely related to the Epstein-Barr virus that causes mononucleosis in humans. About 75 percent of people over 30 carry this virus, Speck says. Another family member is thought to cause Kaposi's sarcoma, a cancer most commonly seen in AIDS patients. The extremely common herpesvirus simplex 1, the cause of cold sores, is a more distant relative. "These viruses are now legitimate candidates for initiating human vascular disease," Virgin says. "It's a possibility that deserves further investigation."
Despite repeated efforts, researchers have never been able to prove or disprove the hypothesis that viruses trigger human vascular disease. A middle-aged person with atherosclerosis will have been exposed to hundreds of viruses, making it very difficult to link the vascular disease to a particular infection, Virgin says. Until someone catches a virus in the act of damaging a human artery, most researchers will remain skeptical that it can ever happen. Knowing which viruses to look for will aid the search tremendously, he says.
Note: For more information, refer to K.E. Weck, et.al., "Murine g-herpesvirus 68 causes Severe Large- vessel Arteritis in Mice Lacking Interferon-g Responsiveness: A New Model for Virus-induced Vascular Disease," Nature Medicine, Vol. 3 (12) pp. 1346-1353, December 1997.0
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