Fatigue Syndrome and Depression
A twenty-year search by a top Japanese virologist has led to the discovery that protein
from the quiet smoldering of a common virus can cause Central Nervous System
disease and mood disorders
BALTIMORE, MD (June 22, 2008)- 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.
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 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 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.
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 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
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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