Researchers at Johns Hopkins have uncovered how a majority of the genetic changes in the hepatic-C virus, the most common cause of liver disease, allow it to evade the body's immune system during infection. Hepatitis C infection can lead to cirrhosis, cancer and even death. In a series of experiments that describe the virus' transition from an acute to chronic infection, the Hopkins team found that one-half of the virus' changes in its genome are in sites under attack by the body's immune system. As the virus evolves and these changes weaken the body's immune response, a second set of changes at other sites in the genome are reverting back to an "ancestral" set of amino acids.

"We think this piecemeal exchange is helping the virus evade the body's immune system," says study investigator and infectious disease specialist Stuart Ray, M.D., an associate professor at The Johns Hopkins University School of Medicine. "In a newly infected person, the virus may need to adopt new mutations to escape recognition by the immune system's T cells, which fight infection, but it may need to lose the mutations that had protected it in someone else. Despite pressure to change, the virus is always is restoring its shape."

The Hopkins findings, published in a pair of studies in the Journal of Experimental Medicine this week, are believed to be the first description of the precise genetic changes taking place in the virus during the acute phase of infection, when hepatitis C initially escapes the body's defenses and establishes itself in the body. As the infection moves into the chronic stage, the immune response becomes weak and less effective, but until now, no one could explain exactly why.

A second, related experiment produced similar findings when the Hopkins team partnered with researchers in Ireland to perform what is believed to be the first comparison of genetic changes across multiple genes in strains from chronically infected people to the or
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Contact: David March
dmarch1@jhmi.edu
410-955-1534
Johns Hopkins Medical Institutions
9-Jun-2005

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