Interferon-inducible gene expression in chimpanzee liver infected with hepatitis C virus.

The molecular host response to hepatitis C virus (HCV) infection was examined by isolation of HCV-induced genes from a cDNA library constructed from chimpanzee liver during the acute phase of hepatitis C. Two cDNA clones, 130-7 and 130-51, were obtained by differential hybridization with cDNA probes prepared from poly(A)+ RNAs of infected and uninfected livers. Northern blot analysis revealed that the 130-7 and 130-51 cDNAs were expressed as 1.5- and 1.0-kb products, respectively, in chimpanzee liver and that their induction rates of the two were 20 and 4, respectively. Nucleotide sequence analyses of these cDNA inserts showed that the sequence of cDNA 130-7 was that of a class I major histocompatibility antigen and that the sequence of cDNA 130-51 was 98% homologous with a human interferon-inducible mRNA. These results suggest that HCV infection may actively induce interferon, which in turn induces the expressions of these interferon-inducible genes. Furthermore, the high expression of HLA class I antigen in the acute phase of hepatitis C suggests that liver cell injury in HCV infection may be mediated by cytotoxic T cells that recognize viral antigen in association with HLA class I antigen.