UPTON, NY -- As part of an ongoing effort to understand how viruses infect cells, scientists at the U.S. Department of Energy's Brookhaven National Laboratory have deciphered the molecular-level interaction between coxsackievirus -- which infects the heart, brain, pancreas, and other organs -- and the human cell protein to which it attaches.

This work, published in the October issue of Nature Structural Biology, may lead to improved ways to thwart viral infections, and may help scientists design virus-based vehicles for gene therapy.

The study reveals that the receptor protein for coxsackievirus (known as coxsackievirus-adenovirus receptor, or CAR) forms pairs on the surface of human cells, with two adjacent CAR receptors attached to one another below the surface of the cell membrane. When coxsackievirus binds to the human cell, it forms bonds with both receptors of the pair.

"This arrangement is advantageous for the virus," says Brookhaven biologist Paul Freimuth, one of the study's authors. "The binding becomes almost irreversible, because both bonds would have to reverse simultaneously to release the virus. That increases the likelihood that the virus will infect the cell."

The structural studies also reveal that the binding sites on the coxsackievirus are "cleverly" hidden from the body's immune system, which produces antibodies to fight infections. "If you think of the virus as a golf ball, the binding sites that recognize the receptor are inside the dimples," Freimuth says. "Antibodies can't fit into the indentations, but the receptor is a slender molecule that can fit in."

Both of these features -- hidden binding sites and simultaneous binding to multiple receptors -- are shared by other viruses in the same family, including the virus that causes polio and rhinovirus, one cause of the common cold and other respiratory and gastrointestinal infections.

"It's a very clever arrangement that these viruses have work
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Contact: Karen McNulty Walsh
kmcnulty@bnl.gov
631-344-8350
DOE/Brookhaven National Laboratory
25-Sep-2001