Genomic analysis of the host response to hepatitis C virus infection.
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-alpha response that correlated with the magnitude and duration of infection. Transient and sustained viral clearance were uniquely associated with induction of IFN-gamma-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.
Su
Andrew I
AI
Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA.
Pezacki
John P
JP
Wodicka
Lisa
L
Brideau
Amy D
AD
Supekova
Lubica
L
Thimme
Robert
R
Wieland
Stefan
S
Bukh
Jens
J
Purcell
Robert H
RH
Schultz
Peter G
PG
Chisari
Francis V
FV
D000818:Animals; D017951:Antigen Presentation; D005227:Fatty Acids / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D006526:Hepatitis C / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007372:Interferons / Q000096:biosynthesis; D050356:Lipid Metabolism; D002679:Pan troglodytes; D012093:Replicon; D014158:Transcription, Genetic; D014162:Transfection; D014766:Viremia / Q000235:genetics / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects
D005227:Fatty Acids; D007372:Interferons