Experimental infection of chimpanzees with hepatitis A virus.

The susceptibility of chimpanzees to viral hepatitis type A was examined with immine electron microscopy. Of four seronegative infant chimpanzees, two were inoculated with a hepatitis A acute-phase stool filtrate rich in 27 nm virus-like hepatitis A antigen (HA Ag) particles, and two were inoculated with an HA Ag-negative preinfection stool filtrate. One of each pair of chimpanzees was inoculated intravenously, the other orally. One month later both chimpanzees that had received the HA Ag-positive filtrate developed biochemical, histologic, and clinical evidence of acute viral hepatitis. HA Ag particle (27 nm) were detected in their stools by immune electron microscopy; particle shedding followed a pattern similar to that in human volunteers. Immune electron microscopy also showed that antibody HA Ag had developed in the convalescent-phase sera of the infected chimpanzees. Control animals remained free of illness at this time but did develop hepatitis three to five weeks after exposure to the two infected chimpanzee-. The infectious inoculum was titrated in two additional seronegative chimpanzees. It was concluded that hepatitis a can be successfully transmitted to seronegative chimpanzees. Moreover, these studies provide further evidence that the 27-nm virus-like HA Ag particle is the etiologic agent of viral hepatitis type A.