Kenneth R. Berquist

Viral hepatitis, type B, in experimental animals.

Evidence of natural infection with hepatitis B virus (HBV) in chimpanzees was followed by demonstration that this species provides a highly sensitive animal model system for experimental type B hepatitis. With rare exceptions, inoculation of sero-negative chimps with materials containing infectious HBV produces serologic evidence of infection including appearance of circulating hepatitis B surface antigen (HBs Ag) and subsequently development of antibody to HBs Ag and hepatitis B core antigen. Serum enzyme elevations indicative of liver damage occurred in 31 of 46 aminals infected to date. The antigenic subtypes of HBV in the inocula breed true in the infected animals, and HBV titers of sera containing the adw and ayw subtypes have been established as 10(7.5) infectious units/ml. Rhesus monkeys also provide a valuable animal model for type B hepatitis, but they appear to be less sensitive than chimps, and they do not develop evidence of liver damage.

Antiviral Effects of Virazole in Chronic Hepatitis B Surface Antigen-Seropositive Chimpanzees

Virazole (Ribavirin, ICN 1229), a broad-spectrum, antiviral chemotherapeutic agent was used to treat two adult chronically hepatitis B surface antigen (HBs Ag)-seropositive chimpanzees. No significant change in serum hepatitis B surface antigen was noted and no adverse reactions were observed. The role of viral replication in the chronic carrier state of hepatitis B is discussed.

Immunofluorescent Localization of Hepatitis B Antigens in Chimpanzee Tissues

Three chimpanzee chronic carriers of hepatitis B surface antigen (HBs Ag) were examined by immunofluorescent techniques to determine the localization of HBs Ag and hepatitis B core antigen (HBc Ag) in their tissues. All specimens were quick-frozen in liquid nitrogen and stored at -70degrees until sectioned. Frozen sections were prepared and stained for examination by fluorescent microscopy. For staining, anti-HBs and anti-HBc labeled with fluorescein isothiocyanate were used. HBs Ag was found in the liver of all three animals. In two animals which were necropsied, HBs Ag was detected in other tissues, e.g., lymph nodes, spleen, and kidney. Specificity of these tests was demonstrated by blocking with purified HBs Ag. Examination of various tissues revealed HBc Ag only in the liver. 32 samples of liver, from different sites from one chimpanzee, were examined and all were positive for both HBs Ag and HBc Ag. The finding of HBc Ag only in the liver further supports the assertion that the liver is the sole site of replication of hepatitis B virus in chronic carriers.