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Single Amino Acid Change In Herpes Virus Prevents It From Infecting Neurons

Date:
July 15, 1999
Source:
University Of Chicago Medical Center
Summary:
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.

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 moving on to the next cell. It does this by tricking the cell into entering S phase, a time in the cell cycle when it prepares for cell division.

"During S phase, the cell duplicates its chromosomes and generates a large number of different proteins that will get passed on to the daughter cell," explains Chip Van Sant, Ph.D., a research associate in Dr. Roizman's lab and co- author of the paper. "By nudging the cell into this phase, the virus takes advantage of the protein enriched environment by scavenging the proteins to build more viral particles."

Once the cell is in S phase, the virus collects the proteins it will need to make copies of itself until it bursts through the cell and infects its neighbors. The process continues until the virus enters a neuron.

Previously, Van Sant and another research associate, Yasushi Kawaguchi, Ph.D., found that the viral protein ICP0 binds to a cellular molecule called cyclin D3, stabilizing it and prolonging its life span in the cell.

To test the theory that ICP0 is crucial for infecting neurons, Van Sant created mutant herpes viruses in which ICP0 protein differed from normal ICP0 proteins by a single amino acid. When he injected this mutant virus into the epidermal cells of mice, the virus was unable to migrate to the neurons.

"This is amazing because we've shown that taking over cyclin D3 affects viral pathogenesis, which adds to a growing theme that the virus usurps many of the cell's normal functions for its own use. The more we know about what the virus is after, the greater the opportunities to block it from achieving its aims," says Van Sant.

The study was aided by grants from the National Cancer Institute and the National Institute of General Medical Sciences.


Story Source:

The above story is based on materials provided by University Of Chicago Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

University Of Chicago Medical Center. "Single Amino Acid Change In Herpes Virus Prevents It From Infecting Neurons." ScienceDaily. ScienceDaily, 15 July 1999. <www.sciencedaily.com/releases/1999/07/990715063204.htm>.
University Of Chicago Medical Center. (1999, July 15). Single Amino Acid Change In Herpes Virus Prevents It From Infecting Neurons. ScienceDaily. Retrieved July 24, 2014 from www.sciencedaily.com/releases/1999/07/990715063204.htm
University Of Chicago Medical Center. "Single Amino Acid Change In Herpes Virus Prevents It From Infecting Neurons." ScienceDaily. www.sciencedaily.com/releases/1999/07/990715063204.htm (accessed July 24, 2014).

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