COXSACKIEVIRUS & HEART DISEASE
******************************
A ProMED-mail post
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[see also:
Viral myocarditis/HFMD - Malaysia (Sarawak)            20000329222425
Viral myocarditis/HFMD - Malaysia (Sarawak) (02)     not yet archived]

Date: Thu, 30 Mar 2000 15:26:26 -0500
From: Robertson, George <GRobertson@bioreliance.com>
Source: Canadian press, [edited]
<http://news.excite.ca/news/ap/000330/01/health-heart-disease,bgt>


Link between common virus and heart failure discovered 

The gene that allows one of most common and highly-contagious viral
infections to trigger deadly heart disease has been discovered by
researchers at Princess Margaret Hospital's Ontario Cancer Institute,
Toronto General Hospital, the AMGEN Research Institute and University of
Toronto's Heart & Stroke/Richard Lewar Centre of Excellence.  Researchers
discovered the role of a key gene called p56Ick that allows a common
coxsackievirus to attack the heart causing heart failure and even death in
some patients. The finding paves the way for future research into how to
better predict who is at serious risk of cardiovascular disease and how to
prevent it, and is reported in today's issue of Nature Medicine. The
research was funded in part by Amgen, the Medical Research Council of
Canada and the Heart and Stroke Foundation of Canada.  

"This finding could lead to a much more targeted way to determine who is at
very high risk for developing heart disease," said senior author and world
expert on inflammation and heart disease Dr. Josef Penninger, an
immunologist at Princess Margaret Hospital's Ontario Cancer Institute and
the AMGEN Institute and a member of the Departments of Medical Biophysics
and Immunology at the University of Toronto. "Rather than guessing at
potential risk factors, we will be able to say much more definitively who's
likely to get heart disease by testing for the presence of one gene."
According to the paper's lead author Dr. Peter Liu, a cardiologist at
Toronto General Hospital and Director of the Heart and Stroke/Richard Lewar
Centre of Excellence at the University of Toronto, "this finding may also
open the door to new treatment strategies for virus-induced heart failure.
We are thrilled at the potential of these findings."  NO CURE 

Coxsackieviruses are part of an extremely common family of viruses that
live in the human digestive tract and are highly contagious. An estimated
70 percent of the population has been exposed to Coxsackievirus B which
spreads easily from person to person like the flu. There is no vaccine
against coxsackievirus infections (in contrast to its famous cousin, the
polio virus) and no cure. Although the most common result of a
coxsackievirus infection is the flu, they can also cause pancreatitis
leading to diabetes, arthritis, meningitis and myocarditis (an infection of
the heart muscle) leading to heart failure. Children with coxsackieviral
myocarditis can develop flu-like symptoms followed quickly by heart failure
and death. Coxsackievirus B can be detected in the hearts of between 30 and
50 percent of all adults with heart failure due to heart muscle weakness, a
condition that frequently leads to the need for a heart transplant. In a
mouse model, Drs. Penninger and Liu discovered that the difference between
suffering minor flu symptoms and developing heart disease comes down to the
p56Ick gene.  

"Nearly all of us have been exposed to Coxsackievirus B at some time in our
lives and experienced nothing more than the flu," said Dr. Liu. "However,
in those people at risk, the p56Ick gene helps the virus to trigger the
immune system to turn against the heart muscle. Without the p56Ick gene,
the virus cannot replicate and remains relatively harmless."  

HITCH-HIKING VIRUS The body's immune system is designed to recognize
foreign agents and destroy them. When infection is detected by the body,
the immune system, or T-cells, sets out to attack it. Coxsackievirus B uses
t-cells to hitch a ride into the system. When a coxsackievirus infection
causes mild flu-like symptoms and inflammation, T-cells head to the site of
the infection to fight it. As T-cells travel to the heart to fight off the
infection, the virus goes along for the ride on the back of T-cells,
ultimately reaching the heart. Once in the heart, the virus stimulates the
immune system to attack the heart muscle. Drs. Penninger and Liu engineered
special "knockout mice" that lacked the p56Ick gene. When injected with
coxsackievirus B, mice with the p56Ick gene developed severe inflammation
of the heart muscle and die from heart failure. Those mice without p56Ick
were completely immune to heart disease despite being exposed to large
doses of the virus leading to the conclusion that p56Ick is the crucial key
gene that controls the effect the virus has on the heart.  Heart disease is
the number one killer in the Western world and according to Dr. Liu, one in
eight cases of heart failure may be blamed on coxsackievirus B. 

Last year, Dr. Penninger led a research team in the first discovery of link
between heart disease Chlamydia infections, one of the most common
infections contracted by humans. With that study, Dr. Penninger and his
colleagues found that the best predictor of future heart disease might not
be lack of exercise, poor diet or high cholesterol, but inflammation.  "For
years we have associated various risk factors with heart disease including
high cholesterol levels, smoking, stress, high blood pressure and obesity,"
said Dr. Liu, "and now infections are thought to play a very critical role
in many heart diseases. In this study we have shown for the first time how
a common infection with coxsackievirus B may cause severe heart disease. "
"Coxsackievirus B is just one in a large family of related viruses that
cause a great number of symptoms, from common colds and diarrhea, to
paralysis and even diabetes in children," said Dr. Penninger. "Now that we
have discovered the cellular factor that controls the body's reaction to a
coxsackievirus B infection, we can build on it to find the genetic trigger,
and eventual block for, the viruses that cause the common cold, diabetes or
diarrheas as well."  

PREVENTING HEART DISEASE The finding may pave the way for the future
engineering of antibiotics to prevent, treat or even cure cardiovascular
disease by blocking the effects of the virus. "It's not the virus that
kills you, its your body's response to the virus that kills you," said Dr.
Penninger. "We found that you don't need to worry about stopping the virus
at all. All you need to do is change one single molecule in the body and
the virus can harmlessly come and go with no effect on the host. In effect
we cure the disease by preventing its action in the first place without
doing anything at all to the virus itself."  

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