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Eliminating Cell Receptor Prevents Infections in Animal Study
Date:7/22/2009

s in cell cultures. They may attack specific tissues in humans or animals, but without binding to the cellular receptors identified in cultured cells. For instance, adenovirus infects the liver, but it bypasses identified adenovirus receptors in that organ. Instead the virus engages in complicated interactions with blood proteins and unidentified molecules in the liver.

Therefore, Bergelson and colleagues set out to discover whether CVB interacts with its receptor to cause pancreatitis and myocarditis in a special breed of mice. By manipulating genes in the pancreas and heart that generate CAR in those organs, Bergelson's team prevented the mice from forming CAR at those sites. Subsequently, those mice had virus levels in the pancreas a thousand times smaller than in control animals, and had significantly less tissue damage and inflammation. A similar protective effect occurred in the mice designed to lack CAR in their heart cells.

The results indicate that CAR is the receptor used by coxsackieviruses to infect the heart and pancreas and to cause direct injury to tissues. In some patients, recovery from coxsackievirus infection is followed by slowly progressive inflammation and heart damage. Bergelson's lab is interested in whether this long-term damage also depends on virus interaction with CAR.

Grants from the National Institutes of Health, the American Heart Association and the ACVP/STP Coalition for Veterinary Pathology Fellows supported this research. Bergelson's co-authors were Nicole L. Kallewaard, Ph.D., Lili Zhang, Jin-Wen Chen, Ph.D., and Marta Guttenberg, M.D., all from Children's Hospital; and Melissa D. Sanchez, D.V.M., Ph.D., of the University of Pennsylvania School of Veterinary Medicine.

Kallewaard et al, "Tissue-specific deletion of the coxsackievirus and adenovirus receptor (CAR) protects mice from virus-induced pancreatitis and myocarditis," Cell Host and Microb
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SOURCE The Children's Hospital of Philadelphia
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