A Protein from a Common Smoldering Virus Linked to Chronic Fatigue Syndrome and Depression

Mon Jun 23, 2008 10:28am EDT

* Reuters is not responsible for the content in this press release.

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.


Kristin Loomis
Executive Director
HHV-6 Foundation
Phone: 805-969-1174

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