To find an effective treatment for hepatitis C, which chronically infects nearly 200 million people worldwide, researchers need to understand how the virus is able to avoid destruction by the immune system. Hepatitis C persists in the body for decades after an initial infection, often causing so much liver damage that liver transplantation may be a patients only chance for survival.
Now, scientists at the
In an additional paper, appearing in the current Journal of Virology and available now online, the UT Southwestern and UTMB researchers demonstrate the critical role played by one of the circuits, known as the RIG-I pathway, in cellular defense against hepatitis C virus.
The discoveries are particularly important in light of recent promising results from early clinical trials of new investigational drugs that target NS3/4A and both block the reproduction of hepatitis C and nullify its ability to dodge immune defenses, according to Stanley M. Lemon, a senior author on the papers and director of UTMBs NIH-funded hepatitis C research center. At least one protease inhibitor has had extraordinary activity against hepatitis C in human clinical trials, but were going to need to improve on it in a number of ways, including reducing the potential for the virus to become resistant to it, Lemon said. A better understanding of how NS3/4A does its work in blocking the immune response will help make that possible.
Lemons group, including lead author and assistant professor of microbiology and immunology Kui Li, postdoctoral fellows Josephine C. Ferreon, Mitsuyasu Nakamura, Allan C.M. Ferreon and Masanori Ikeda, collaborated with Michael Gale and Eileen Foy of UT Southwestern on one PNAS paper, Immune evasion by hepatitis C virus NS3/4A protease-mediated cleavage of the Toll-like receptor 3 adaptor protein TRIF. Lemon and Li also collaborated with the UT-Southwestern team led by Gale on the second PNAS paper (Control of antiviral defenses through hepatitis C virus disruption of retinoic acid-inducible gene-I signaling), on which Foy is the lead author, and Rhea Sumpter, Jr., Yueh-Ming Loo, Cynthia L. Johnson, Chunfu Wang, and Penny Mar-Fish are co-authors.