By Lisa Seachrist

Washington Editor

BETHESDA, Md. — In the quest for an infectious agent that tricks the body's immune system into attacking its own nerves, causing multiple sclerosis, researchers have always been drawn to the herpes viruses.

Like the waxing and waning of the disease process itself, herpes viruses are capable of infecting, lying quiescent and ultimately reactivating. Stress and infection with another virus serve as triggers for multiple sclerosis (MS) flare-ups as well as herpes virus reactivation. Nevertheless, attempts to link Epstein-Barr virus and cytomegalovirus infections to MS have failed.

However, new evidence from researchers at the National Institute for Neurological Disorders and Stroke (NINDS), in Bethesda, Md., strengthens the association of another herpes virus — human herpesvirus 6 (HHV-6) — with multiple sclerosis.

"We've been down this road many times in the last 50, 60 years," said Steven Jacobson, chief of the viral immunology section at the NINDS. "But we haven't had the technology in the past, and that technology is pointing us in a new direction, a very exciting direction."

As many as 350,000 Americans suffer from MS — a disease in which the body's own immune system destroys the myelin sheath, causing muscle weakness, blurred vision, balance problems and loss of sensation. The disease strikes women more often than men, although the symptoms and severity vary from patient to patient.

The most common form of MS is the relapsing-remitting type, which is characterized by flare-ups. A less common form is chronic progressive MS, where symptoms steadily worsen. Either version can lead to disability and paralysis.

Although a tremendously common virus in the U.S. ,where 90 percent of adults have been infected, HHV-6 was only identified a decade ago as the cause of roseola — a skin rash and fever that strikes infants. Its genetic sequence was completed last year.

In 1995, HHV-6 was shown to inhabit the plaques of multiple sclerosis lesions — regions of nerves that have lost the protective myelin sheath that ordinarily surrounds them.

Jacobson and his colleagues screened the serum of 102 volunteers, 36 of whom suffered from multiple sclerosis. As the researchers reported in the December issue of the journal Nature Medicine, of the 22 individuals with the relapsing-remitting form of the disease, 73 percent had an increased immune response to an early antigen of HHV-6 compared with 18 percent of the normal volunteers.

Disease "Snapshot" Found

"The increased IgM — or early antibody — response is well above normal, and these patients showed no increase in IgG antibodies to HHV-6," said Jacobson. "And while MS patients often have increased antibodies to a number of different viruses, we found no increase in antibody responses to either Epstein-Barr or cytomegalovirus. These findings are consistent with a persistent infection being implicated with disease."

In addition to the antibody data, the researchers detected HHV-6 DNA in the serum of 15 of the 50 patients — approximately 30 percent — with MS. None of the normal volunteers had HHV-6 DNA — a marker of viral replication — in their bloodstreams.

"What we may have found is a snapshot of the disease process itself," Jacobson said. "If that is the case, we could potentially one day use viral replication as a marker for starting antiviral treatments."

Jacobson noted that beta interferon, which has been approved as a drug for MS, was originally studied as an antiviral agent. Perhaps even more telling, the product is effective in approximately 30 percent of cases. "This could potentially be clinically significant," he said.

Jacobson noted that his group has already begun a large-scale study of the serum of MS patients, normal controls and patients with other autoimmune disease to assess the levels of HHV-6 antibodies and HHV-6 viral replication in a larger population.

While the fact that HHV-6 is so widespread and MS is a relatively rare disease seems paradoxical, Jacobson noted that the answer may lie in the interaction between the infective agent and the genetic makeup of the infected individual.

"For such a ubiquitous virus to be associated with a disease, we would have to envision a situation where a person has a genetic susceptibility for the disease," Jacobson said. "That sort of rules out finding 'the virus that causes MS.' It is a complex interplay between genes and the environment rather than a genetic or viral cause of the disease." *

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