Expression profiling of liver cell lines expressing entire or parts of hepatitis C virus open reading frame.
Although hepatitis C virus (HCV) is a causative agent of liver diseases, its mechanism of pathogenesis is still unclear, mainly because of the lack of adequate cell culture systems to support HCV infection and replication. In this report, we describe development and characterization of human hepatoma cell lines constitutively expressing entire (Hep394) or parts (Hep352, Hep3294) of the HCV open reading frame (ORF). The viral and cellular proteolytic machinery involved in the viral precursor processing was consistently functional, and processed HCV proteins were synthesized in these established cell lines. By using a cDNA microarray analysis coupled with semiquantitative reverse-transcription polymerase chain reaction (RT-PCR), we identified 12 genes up-regulated and 4 genes down-regulated in Hep394 cells. With regard to genes related to cell growth regulation, we found up-regulation of forkhead transcription factor FREAC-1, poly (A) binding protein PABP2, and Ras suppressor Rsu-1. Another category of changes in gene expression includes MHC antigens, which play an important role in the T-cell-mediated immune reaction in the liver. In conclusion, functional genomic approaches comparing expression among the different cell lines expressing parts of the HCV genome may promote our understanding of the molecular basis of pathogenicity of HCV infection.
Aizaki
Hideki
H
Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.
Harada
Takashi
T
Otsuka
Motoyuki
M
Seki
Naohiko
N
Matsuda
Mami
M
Li
Yue Wei
YW
Kawakami
Hayato
H
Matsuura
Yoshiharu
Y
Miyamura
Tatsuo
T
Suzuki
Tetsuro
T
D006528:Carcinoma, Hepatocellular; D004268:DNA-Binding Proteins / Q000235:genetics; D051858:Forkhead Transcription Factors; D015870:Gene Expression; D020869:Gene Expression Profiling; D016174:Hepacivirus / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms; D016366:Open Reading Frames; D039103:Poly(A)-Binding Protein II / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C098521:FOXF1 protein, human; D051858:Forkhead Transcription Factors; D039103:Poly(A)-Binding Protein II; D015534:Trans-Activators; D014157:Transcription Factors; C076224:RSU1 protein, human