Serial transmission of hepatitis B like non-A, non-B hepatitis and associated markers to chimpanzees successfully immunized against HBV.

In order to demonstrate that the HBV like strain of NANB hepatitis bred true as non-B together with its associated markers, 2 chimpanzees with high titer anti-HBs (45 and 125 AUSAB RU respectively) immunized with the Pasteur HB vaccine received 1 ml IV of a NANB inoculum. Two neighbour captive animal served as controls. The inoculum was the serum of a leukemic patient in remission for over 3 years with NANB chronic active hepatitis which serum contained HBV like particles and was found positive for NANBe Ag and anti-NANBc whereas in the liver typical numerous "SHIMIZU" dense soft edge aggregated intranuclear structures were demonstrated by electron microscopy. After 4 weeks portal inflammation and hepatocyte necrosis with significant aminotransferase elevation lasting for over 10 weeks developed in the 2 infected chimpanzees. No change in anti-HBs titer was seen and HBs, HBc, HBe Ag and/or AB could neither be detected in serum by RIA nor in liver by immunofluorescence during the 6 month follow up period. By contrast NANBc Ag became clearly demonstrable by immunofluorescence in the liver nuclei together with anti-NANBc in the serum after the 6th week and both persisted for over 4 months. Double unit structures similar to those of NANB/F strain were demonstrable in the cytoplasm at the acute phase. None of these changes was seen in the two control animals. Inoculation of the acute phase serum in the 2 previous control animals was again followed by the same sequence of events. Hybridization studies with HBV DNA of liver biopsies of infected chimps were negative.