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.
contact sources : Matthias Gromeier , 919-668-6205
Dufresne AT, Gromeier M.
A nonpolio enterovirus with respiratory tropism causes poliomyelitis in intercellular adhesion molecule 1 transgenic mice.
Proc Natl Acad Sci U S A. 2004 Sep 7 [Epub ahead of print]
© 2001-2004 Duke University Medical Center
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