Follow-up of hepatitis C virus infection in chimpanzees: determination of viraemia and specific humoral immune response

Abstract

Chimpanzees were inoculated intravenously with the H strain of hepatitis C virus (HCV), and analysed for viraemia using the polymerase chain reaction and for a humoral immune response using first and second generation anti-HCV ELISAs and an immunoblot assay (4-RIBA). In all seven chimpanzees studied, viraemia occurred several weeks before a significant increase in serum alanine transferase (ALT) activity, whereas the first circulating anti-HCV antibodies became detectable at the time of significant increase in ALT levels, provided the second generation ELISA or 4-RIBA was used. On the basis of the duration of viraemia the chimpanzees studied could be assigned to two different groups: those in which viraemia disappeared in conjunction with or shortly after seroconversion, and those remaining viraemic for many weeks after the appearance of antibodies. The clearance of HCV from the circulation did not correlate with the antibody pattern determined using 4-RIBA, i.e. the HCV-specific assays currently available do not enable us to predict whether an infected chimpanzee will develop persistent viraemia. Only two of the seven chimpanzees analysed developed anti-core protein (c-22) antibodies, which appeared at the same time as the first ALT peak, whereas all animals developed antibodies to the non-structural protein, c-33, and these antibodies persisted.