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Common Cold Virus Can Cause Polio In Mice When Injected Into Muscles

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Duke Health News 919-660-1306

DURHAM, N.C. -- Virologists at Duke University Medical
Center have discovered that, under the right conditions, a
common cold virus closely related to poliovirus
can cause polio in mice.

The researchers injected a cold virus called Coxsackievirus
A21 into mice that were engineered to be susceptible to this
particular virus. However, instead of developing a cold, the
mice unexpectedly displayed paralytic symptoms characteristic
of polio. The researchers determined that administering the
virus directly into muscles, instead of the virus's normal home
in the nasal cavity, was critical for development of polio.

The findings challenge traditional views as to what defines
a poliovirus, said Matthias Gromeier, M.D., a Duke virologist
and senior author of the study.

"In principle, Coxsackieviruses could cause polio in
humans," said Gromeier. "We are in the process of eradicating
polio worldwide, but if we eliminate the poliovirus and cease
polio vaccinations, our immune systems wouldn't produce
antibodies against polio, and Coxsackievirus could
theoretically fill the niche of eradicated polio" he said.

Results of the study will be published in the Sept. 6, 2004,
issue of the Proceedings of the National Academy of
Sciences.

Until now, it has been widely accepted that Coxsackievirus
and poliovirus cause distinct illnesses because they bind to
different docking sites, called receptors, on host cell
surfaces. The current study turned that belief on its head,
said Gromeier. Poliomyelitis has long been regarded as the
signature of poliovirus, a virus that recognizes and binds to
the CD155 receptor. However, the mice were genetically
engineered to have only the Coxsackie A21 receptor, called
ICAM-1, and they did not have the poliovirus receptor. Still,
when the mice were injected with Coxsackievirus, it initiated
infection through the ICAM-1 receptor, and caused symptoms of
polio.

The manner in which the mice were infected with
Coxsackievirus facilitated its unusual behavior inside the
body, the study showed. The mice were injected with
Coxsackievirus into their calf muscles, an unusual route of
entry. Following the injection, the mice began to display
symptoms of polio, including an abnormal gait, dropfoot, and
lower hind limb paresis.

The researchers were left wondering how this intramuscular
portal of entry could affect the virus's ability to access the
types of cells normally infected by polio.

In studying the virus' action within infected mice, they
found that the virus traveled from the calf muscle where it was
injected to the central nervous system along "motor neuron
axons." Such axons extend from the central nervous system to
muscles throughout the body and convey commands for muscle
movement. The site in the muscle where axons physically attach
is called a neuromuscular junction. These junctions likely
served as the cold virus' portal of entry into the nervous
system.

"We gave the coxsackievirus a distinct advantage by
injecting it directly into muscle, where it had direct access
to the kinds of nerve cells polio normally attacks," said
Gromeier. "The resulting polio symptoms were milder than those
caused by the poliovirus, but it was polio nonetheless."

Such a subtle change in entry mode significantly changed the
virus' behavior, and therein lies one of the greatest dangers
associated with viruses, said Gromeier.

Viruses are extremely adaptable and they can alter
themselves dramatically based upon their environment.
Coxsackievirus A21 is one of a large group of cold viruses that
are genetically very similar to polioviruses.

"Our study reveals how similar these viruses actually are,"
he said. "It is fascinating that a minor change such as
injection site may cause a harmless cold virus to attack the
central nervous system."

Gromeier's team is now collaborating with the Centers for
Disease Control to test numerous Coxsackievirus samples from
patients around the world. Their goal is to determine which
genetic features of the Coxsackievirus induce polio and under
what conditions.

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