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Scripps Research Institute scientists achieve most detailed picture ever of key part of hepatitis C
Date:11/28/2013

it typically causes few or no symptoms when it infects someone. In many cases it establishes a long-term infection of the liver, damaging it slowly for decadesuntil liver cirrhosis and/or cancer develop. "It's known as a 'silent killer'," said Law. Expensive and risky liver transplantation is often the only way to save a patient's life. Some antiviral drugs are useful in treating and even curing chronic HCV infection, but the more effective ones are extremely expensiveand most HCV-positive people don't even know that they're infected and need treatment.

An HCV vaccine could put an end to the global pandemic by preventing new infections. "It could be given to people when they're young and healthy, and they'd never have to worry about developing HCV-related liver diseases," said Ward.

However, like HIV and some other viruses, HCV uses several effective countermeasures to evade the immune system. These include fast-mutating regions on the E2 protein, which ensure that antibodies to one HCV strain typically are ineffective against other strains. The E2 protein also coats itself with relatively antibody-proof sugar molecules.

To defeat these viral countermeasures, scientists have wanted to "see" the high-resolution atomic structure of HCV, particularly E2 and its CD81 receptor binding site, which does not vary much from strain to strain. In recent years, Law's laboratory and others have isolated antibodies that manage to grab hold of this relatively conserved region of E2, thereby blocking the infectivity of a large fraction of HCV strains. In principle, a vaccine that prompts the body to make similar antibodies would effectively and cheaply immunize people against most of their risk of HCV infection.

Unruly E2

But precisely mimicking these antibody-binding sites in a vaccine means first determining their high-resolution structures, which has been difficult even to attempt. "Usually if you try to express the E2 protein
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Contact: Mika Ono
mikaono@scripps.edu
858-784-2052
Scripps Research Institute
Source:Eurekalert  

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