Scripps Florida scientists develop a process to disrupt hepatitis C virion ...( Using genetic mapping and biochemica...),Health

Using genetic mapping and biochemical analyses, the authors were able to show that their deletion altered a phosphorylation signal controlling the switch from RNA replication to virus particle assembly. This signal was attributed to the activity of a cellular kinase that when inhibited by genetic or chemical means led to a reduction in infectious virus production without altering HCV RNA replication.

These data provide the first evidence for a function of domain III of NS5A and implicate NS5A as an important regulator of the RNA replication and virion assembly of HCV, Tellinghuisen says. The ability to uncouple virus production from RNA replication may be useful in understanding HCV assembly and may become therapeutically important.

Charles M. Rice, head of the Center for the Study of Hepatitis C at Rockefeller University, comments, This is a spectacular advance linking a specific phosphorylation event by a cellular kinase to hepatitis C virus assembly. Remarkably, the target is a viral nonstructural protein, NS5A, and the data point to a pivotal role for this protein in regulating RNA amplification and infectious virus production. These new data make this multifunctional protein an even more attractive target for developing new anti-virals for treating hepatitis C.

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