Experimental Infection of Chimpanzees with Hepatitis A Virus

Abstract

The susceptibility of chimpanzees to viral hepatitis type A was examined with immune 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 Agnegative 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 particles (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 to 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 chimpanzees. 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.