A Protein From A Common Smoldering Virus Linked To Chronic Fatigue Syndrome And Depression

Main Category: Depression
Also Included In: Psychology / Psychiatry;  Infectious Diseases / Bacteria / Viruses
Article Date: 24 Jun 2008 - 5:00 PDT

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A study suggests that a "smoldering" central 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.

Support for Dr. Kondo's claim came from Stanford University's Jose Montoya who announced at the same conference that the antiviral drug Valcyte, shown to be effective against HHV-6, resulted in an improvement in the cognitive functioning of CFS patients, although not a complete resolution of their fatigue. 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.

A Debilitating Disorder

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, in 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.

Novel Herpesvirus Protein is Associated with Altered Nervous System Cell Activity and Chronic Fatigue Syndrome and Depression

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 health 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.

Traditional Viral Tests May Overlook Important Disease Causing Processes

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 to 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 for direct evidence of the virus are useless," she added. New ultra-sensitive 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

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.

HHV-6 Foundation