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Research details how a virus hijacks cell signals to cause infection

A common virus that causes meningitis and heart inflammation takes a "back door" approach to evade natural barriers, then exploits biological signals to infect human cells. Broadening knowledge of how viruses cause infection, a new study describes elaborate methods that the virus has evolved to bypass the body's defenses.

"This study helps to explain how group B coxsackieviruses infect cells," said Jeffrey M. Bergelson, M.D., a pediatric infectious diseases specialist at The Children's Hospital of Philadelphia. "We found new steps in the virus life cycle."

Dr. Bergelson's study, co-authored with Carolyn B. Coyne, Ph.D., also of Children's Hospital, appears in the Jan. 13 issue of the journal Cell.

Group B coxsackieviruses (CVBs) are common in people, but usually are defeated by the immune system after causing minor infections. However, CVBs may sometimes cause myocarditis, a potentially severe inflammation of the heart in children and adults, as well as viral meningitis, which inflames the lining of the brain. Rarely, the virus may lead to fatal, overwhelming infection in newborns.

CVBs typically reach people in contaminated food or water, with the virus entering cells that line the intestine, called epithelial cells. Just how the virus enters those cells has been puzzling to scientists. Dr. Bergelson previously discovered a cell receptor called the coxsackievirus and adenovirus receptor (CAR) to which the virus attaches itself. However, the CAR remains below the surface of epithelial cells, in a seemingly inaccessible location called the tight junction.

In the new study, Drs. Bergelson and Coyne found that CVBs have evolved an indirect route of attack. The virus first attaches itself to more accessible cell receptors called DAF receptors that lie exposed on the upper surface of epithelial cells.

After attaching itself to a DAF receptor, the virus triggers two signals that open the door to infection. One signal causes
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Contact: John Ascenzi
Ascenzi@email.chop.edu
267-426-6055
Children's Hospital of Philadelphia
12-Jan-2006


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