In the livers of patients whose sera contained antibodies to C100-3 an
tigen (anti-HCV) and hepatitis C virus (HCV) RNA, the presence of HCV
RNA and HCV capsid protein (CP) antigen was demonstrated by in situ hy
bridization and immunohistochemistry, respectively. It was found that
occasional hepatocytes in four of ten livers from patients whose sera
were positive for both anti-HCV and HCV RNA hybridized with antisense
as well as sense oligonucleotide DNA probes, whereas the probes did no
t hybridize with livers from patients whose sera were negative for ant
i-HCV and HCV RNA. Monoclonal antibody against a synthetic oligopeptid
e with amino acid sequence of HCV CP reacted with occasional hepatocyt
es in six of 14 livers from patients whose sera contained these HCV ma
rkers, but not with livers from patients whose sera were negative for
both of them. These results suggest that HCV proliferates within hepat
ocytes since both antisense and sense probes hybridized with cytoplasm
of the hepatocytes and that the virus matures in the cytoplasm as the
capsid proteins were also found in the hepatocytes.