Numerical detection, measuring and analysis of differential interferon resistance for individual HCV intra-host variants and its influence on the therapy response
Issue title: Workshop on Computational Advances in Molecular Epidemiology, Atlanta, GA, USA, November 12, 2011
Affiliations: Division of Viral Hepatitis, Centers of Disease Control and Prevention, Atlanta, GA, USA, E-mails: {kki8, fyv6, izd7, jiv9, yek0}@cdc.gov | Translational Liver Research, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA, E-mail: [email protected]
Note: [] Corresponding author: P. Skums, Division of Viral Hepatitis, Centers of Disease Control and Prevention, 1600 Clifton Road NE, 30329, Atlanta, GA, USA. Tel.: +1 404 639 3803.
Abstract: Hepatitis C virus (HCV) is a major cause of liver disease world-wide. Current interferon and ribavirin (IFN/RBV) therapy is effective in 50%–60% of patients. HCV exists in infected patients as a large viral population of intra-host variants (quasispecies), which may be differentially resistant to interferon treatment. We present a method for measuring differential interferon resistance of HCV quasispecies based on mathematical modeling and analysis of HCV population dynamics during the first hours of interferon therapy. The mathematical models showed that individual intra-host HCV variants have a wide range of resistance to IFN treatment in each patient. Analysis of differential IFN resistance among intra-host HCV variants allows for accurate prediction of response to IFN therapy. The models strongly suggest that resistance to interferon may vary broadly among closely related variants in infected hosts and therapy outcome may be defined by a single or a few variants irrespective of their frequency in the intra-host HCV population before treatment.
