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Adenovirus genes that thwart apoptosis pathways may promote viral latency

Scientists from Emory University are studying the specific genetic mechanisms that allow adenoviruses to establish a persistent, latent infection in individuals that lasts for years after the initial illness has cleared. Their findings could prove useful in improving the safety and efficacy of gene therapy using the adenovirus as a vector to deliver genes into the DNA of cells.

Group C adenoviruses infect more than 85% of individuals early in childhood and are the cause of common respiratory illnesses and infant gastroenteritis. Most of these illnesses resolve within two weeks, but studies have shown that the virus establishes a persistent, latent infection, most likely in T lymphocytes.

Adenoviruses can be profoundly pro- or anti-inflammatory, depending on which viral genes are expressed, explains Emory microbiologist Linda Gooding, Ph.D. When adenoviruses are used as vectors, or vehicles to deliver genes into cells in gene therapy experiments, key anti-inflammatory genes are removed.

"Although the adenovirus is being used for gene therapy, there is a big gap in understanding its life cycle," notes Emory microbiologist Linda Gooding, Ph.D. "The problems with using it as a vector are that the virus is quickly cleared from the system, the same vector cannot be used to readminister the virus because of the immune response, and a virus that is profoundly pro-inflammatory can potentially stimulate a strong inflammatory response by the host."

Since the virus remains in the system for a long period of time and does not seem to trigger disease when reactivated, Dr. Gooding and her Emory colleagues wanted to discover which genes in the natural state of the virus within the population of T lymphocytes help it prevent its own rejection and which genes regulate the anti-inflammatory response. "This could help us improve the usefulness of the adenovirus in gene therapy," she said.

Dr Gooding and graduate student Charlese Garnett studied tis
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Contact: Holly Korschun
hkorsch@emory.edu
404-727-3990
Emory University Health Sciences Center
21-Apr-2002


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