Cut and paste full HCV virus (genome top) does not replicate well in the lab. a version of replicon cut and transferred (bottom) did.
The virus that causes hepatitis C (HCV) has frustrated researchers because of his stubborn refusal to grow in the laboratory. Without an abundant supply of the virus, researchers have had a difficult time determining how the virus causes infection and how to fight it with drugs. Now, a team partly solve this problem. They created a better "replicon" viruslike which produces HCV proteins efficiently without relying on virus itself
thereTwelve years, researchers have identified HCV as the elusive pathogen that was the cause of liver disease in some people who had received blood transfusions. Donated blood is now screened for the virus, reducing the number of new HCV infections. But it is estimated that 1% of the population of the United States has been infected with the virus, which can persist in the body for many years. Over time, it can damage the liver and increase the risk of cancer.
Last year, Ralf Bartenschlager the Gutenberg University in Mainz, Germany, and colleagues reported that they had made an HCV replicon. In other words, they took the HCV genome apart and reassembled it, editing rooms and adding new parts ( Science , July 2, 1999, p. 110). They removed the genes that enable the virus to infect human cells, for example, and nestled in other genes that allow researchers to identify which cells hosts took the replicon.
The replicon system was ineffective, however, the production of the HCV proteins around 1 million host cells. To boost production, a team led by Charles Rice at Washington University in St. Louis rebuilt the system. They studied Bartenschlager data, looking for genetic mutations that might allow the replicon to be more productive. They identified 10 mutations, one of which, called S1179I, was exceptional. Replicon with this mutation produces abundant viral protein in one of the 10 host cells, the researchers report in the December 8 issue of Science .
The innovation has attracted the interest of industrial and academic scientists who are racing to develop treatments for hepatitis C should make it possible "for investigators to study the effects of drugs antivirals and host controls that regulate HCV replication, "says Frank Chisari of the Scripps research Institute in la Jolla, California.
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