Genomic analysis of the host response to hepatitis C virus infection

• DOI: 10.1073/pnas.202608199
• Publication Date: 2002-11-26T17:42:52Z
• Authors: Andrew I. Su; John P. Pezacki; Lisa Wodicka; Amy D. Brideau; Lubica Supekova; Robert Thimme; Stefan Wieland; Jens Bukh; Robert H. Purcell; Peter G. Schultz; Francis V. Chisari
• Keywords: 0301 basic medicine; hepacivirus; transcription, genetic; Pan troglodytes; Transcription, Genetic; Hepacivirus; Transfection; Virus Replication; fatty acids; pan troglodytes; 03 medical and health sciences; Genes, Reporter; lipid metabolism; gene expression profiling; Animals; Viremia; virus replication; Antigen Presentation; viremia; Gene Expression Profiling; Fatty Acids; gene expression regulation; Lipid Metabolism; Hepatitis C; 3. Good health; interferons; antigen presentation; transfection; Gene Expression Regulation; Replicon; Interferons; genes, reporter; hepatitis C; replicon

We have examined the progression of hepatitis C virus (HCV) infections by gene expression analysis of liver biopsies in acutely infected chimpanzees that developed persistent infection, transient viral clearance, or sustained clearance. Both common responses and outcome-specific changes in expression were observed. All chimpanzees showed gene expression patterns consistent with an IFN-α response that correlated with the magnitude and duration of infection. Transient and sustained viral clearance were uniquely associated with induction of IFN-γ-induced genes and other genes involved in antigen processing and presentation and the adaptive immune response. During the early stages of infection, host genes involved in lipid metabolism were also differentially regulated. We also show that drugs that affect these biosynthetic pathways can regulate HCV replication in HCV replicon systems. Our results reveal genome-wide transcriptional changes that reflect the establishment, spread, and control of infection, and they reveal potentially unique antiviral programs associated with clearance of HCV infection.