Fatigue Syndrome and Depression

nervous system (CNS) infection may play a role in conditions that plague millions of

Americans. Kazuhiro Kondo, MD, PhD, of the Jikei University Medical School in Tokyo

identified a novel human herpesvirus-6 (HHV-6) protein present in Chronic Fatigue

Syndrome (CFS) patients but not healthy controls that may contribute to psychological

symptoms often associated with that and other disorders.

“Causes of many chronic diseases are unknown and chronic viral infection is one of the

most suspected candidates,” said Dr. Kondo, who spent 20 years trying to identify the

latent protein responsible for chronic CNS disease and mood disorders.

According to Dr. Kondo, drugs like Valcyte combat active replication but can’t

completely control low level smoldering. “To cure the diseases, we have to reduce the

latently infected virus or prevent its reactivation,” he explains.

Chronic Fatigue Syndrome is a debilitating disorder affecting one to four million

Americans and causing 25 billion dollars a year in economic losses. The primary

symptoms include post-exertional malaise, fatigue, difficulty concentrating, unrefreshing

sleep, muscle and joint pain. High rates of depression co-occur with the disease.

Mostly striking working-age adults, the disease is often triggered by a flu-like episode.

Efforts to find a single pathogen responsible for the disease have, however: failed and the

cause of the disorder is unknown.

Kondo identified a novel HHV-6 protein associated with latent (non-replicating) HHV-6

infected nervous system and immune cells. Transfecting this new protein, called SITH-1

(Small Intermediate Stage Transcript of HHV-6), into nervous system cells called glial

cells, resulted in greatly increased intracellular calcium levels. Increased intracellular

calcium levels are believed to play an important role in psychological disorders and can

contribute to cell death. Expressing the SITH protein though the use of an adenoviral

vector in mouse resulted in manic-like behavior.

A serological study indicated that 71% of CFS patients with psychological symptoms and

none of the healthy controls possessed the antibody against the SITH-1 protein

(p<.0001). Further tests indicated that 53% of depression and 76% of bipolar depression

patients possessed the antibody.

Researchers have suspected that central nervous system infections could contribute to

psychological and central nervous system disorders, and patients with CFS have a much

higher than average rate of depression. This virus spreads cell-to-cell instead of releasing

viral particles into the bloodstream. This has hampered efforts demonstrate that the virus,

plays a role in CNS disease. “This virus persists in the brain and other tissues, but not the

blood, which is where investigators have looked,” says Kristin Loomis, Executive

Director of the HHV-6 Foundation. “Indeed, standard serum PCR DNA tests for direct

evidence of the virus are useless,” she added. ”Better assays are under development,” she

reports, “but currently the best way to identify patients with smoldering HHV-6 infection

is to look for elevated IgG antibody titers.”

Dharam Ablashi, the co-discoverer of the HHV-6 virus, and the HHV-6 Foundation’s

Scientific Director warns that the test won’t be available in the near future. “It may take

years to get the assay validated and into commercial production, but will be worth the

wait. This assay could identify large numbers of patients with CNS dysfunction who

could benefit from antiviral treatment.” The HHV-6 Foundation is working hard to help

scientists like Dr. Kondo develop better assays, says Ablashi.

The HHV-6 Foundation encourages scientific exchanges and provides grants to

researchers seeking to increase our understanding of HHV-6 infection in a wide array of

central nervous system disorders.

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Contact:

Kristin Loomis

Executive Director

HHV-6 Foundation

Phone: 805-969-1174

http://www.hhv-6foundation.org