Genomic response to interferon-α in chimpanzees: Implications of rapid downregulation for hepatitis C kinetics†

摘要: The mechanism of the interferon-alpha (IFN-alpha)-induced antiviral response during hepatitis C virus (HCV) therapy is n o t completely understood. In this study,we examined transcriptional to IFN-alpha in uninfected chimpanzees after single doses chimpanzee, human, or human-pegylated IFN-alpha. Liver and peripheral blood mononuclear cell (PBMC) samples were used for total genome microarray analysis. Most induced genes achieved maximal within 4 hours, began decline by 8 at baseline levels 24 hours postinoculation, a time when high circulating pegylated still present. rapid downregulation may be involved transition between observed phase I II viral kinetics HCV-infected patients. all three forms was similar; thus, reasons previous failures treatment with human not due species specificity partially tissue-specific. A 1778 altered expression twofold more IFN-alpha, 538 950 being unique liver PBMC, respectively. Analysis IFN-gamma responses primary chimpanzee hepatocytes compared as well. overlapping sets hepatocytes. conclusion, largely tissue-specific, rapidly downregulated vivo, which have significant influence on response.