"Persistent hepatitis C virus (HCV) infection is a major cause of liver disease worldwide and is the leading reason for liver transplants in this country," notes NIAID Director Anthony S. Fauci, M.D. "The most prevalent form of HCV in the United States is, unfortunately, the least responsive to available treatments. Moreover, African Americans are even less responsive to therapy than Caucasians," he adds.
The immune system has many ways to detect and fight off invading microbes, and microbes have just as many ways to elude and disarm immune system components. Through a series of experiments on cells grown in the laboratory, Drs. Gale and Lemon defined the strategy HCV uses to evade the host's immune response. As HCV begins to replicate in its human host, it manufactures enzymes, called proteases, which it requires to transform viral proteins into their functional forms. The Texas investigators determined that one viral protease, NS3/4A, specifically inhibits a key immune system molecule, interferon regulatory factor-3 (IRF-3). IRF-3 orchestrates a range of antiviral responses. Without this master switch, antiviral responses never begin, and HCV can gain a foothold and persist in its host.
Next, the scientists searched for ways to reverse the IRF-3 blockade. They applied a protease inhibitor to human cells containing modified HCV. This prevented the virus from making functional NS3/4A and r
Contact: Anne A. Oplinger
NIH/National Institute of Allergy and Infectious Diseases