Changes in gene expression profile by HCV core protein in cultured liver cells: analysis by DNA array assay

In this study, we established hepatitis C virus (HCV) core-expressing mouse liver cells and investigated changes occurring in the gene expression profile accompanied by expression of the viral core protein using DNA array analysis. Both non-transformed and transformed mouse liver cells constitutively expressing the viral core protein were established by DNA transfection, and subjected to DNA array analysis. For the genes judged positive by DNA array, Northern blot analysis was done for corroboration. DNA array analysis revealed one up-regulated gene and three down-regulated genes by expression of the viral core protein in non-transformed liver cells. For the transformed liver cells, four enhanced and five suppressed genes were observed. The Northern blot corroboration analysis clarified two genes, osteopontin precursor and activating transcription factor 4, as being down-regulated by the viral core protein in both non-transformed and transformed liver cells, and three genes, cathepsin D, matrix metalloproteinase 14 and anti-proliferative B-cell translocation gene 2, as being up-regulated by the viral core protein in only transformed liver cells. In conclusion, a total of five genes were identified as viral core protein-responsive ones in the DNA array analysis. Alterations in the expression levels of these genes may be relevant to the viral core-mediated pathogenesis.