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Single amino acid change in herpes virus prevents it from infecting neurons

Researchers at the University of Chicago have found that a single amino acid change in a viral protein called ICP0, stops the herpes virus from entering the nervous system. The finding provides clear evidence of how viruses usurp the machinery of the cells they infect, and reveals a "potential new target for a herpes vaccine or future therapies," says Bernard Roizman, Ph.D., Joseph Regenstein Distinguished Service professor in the department of molecular genetics & cell biology at the University, and lead author of the paper.

Once the virus enters the body, usually through a skin cell, it takes over that cell's protein production by forcing it into overdrive in order to scavenge the cell's proteins for its own use. A single amino acid change in the viral protein that initiates this process leaves the virus unable to take over the protein building mechanism it needs to make copies of itself. Without making multiple copies, it can't invade nearby neurons, report the researchers in the July 9 issue of the Proceedings of the National Academy of Sciences.

From the moment the herpes virus enters the body, it is under attack from the immune system. Its goal is to get from the point of infection to the nearest neuron, where it can't be reached by the body's natural defenses. Once inside the neruon, the virus may remain there (or migrate to the brain where it has the potential to cause encephalitis), for the duration of the host's life, emerging only when the immune system is weakened, to form outbreaks on the lips or genitals.

Even though the distance from the point of infection to a neuron may be shorter than a hair's breadth, the virus needs to pass through several cell layers where it will be vulnerable to attack from the immune system.

To reach the neuron, the herpes virus employs a 'safety in numbers' strategy by using the proteins of the first cell it infects as building blocks to assemble a viral army before m
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Contact: Sharon Parmet
sparmet@mcis.bsd.uchicago.edu
773-702-6241
University of Chicago Medical Center
9-Jul-1999


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