Ultrastructural Changes and Virus‐Like Particles Localized in Liver Hepatocytes of Chimpanzees Infected With Non‐A, Non‐B Hepatitis

Virus‐like particles have been visualized by electron microscopy in the liver hepatocytes of two out of four chimpanzees inoculated with two different human non‐A, non‐B hepatitis‐implicated plasmas. The first two chimpanzees, which were infected with the same inoculum (inoculum A), developed liver histological features characteristic of mild acute viral hepatitis as well as rises in their serum alanine aminotransferase levels. Clusters of intranuclear particles, 22 ± 2 nm in diameter, were visualized in one of every fifth hepatocytes in one of these two chimpanzees. Intracytoplasmic circular membrane fusions, 100 to 350 nm in diameter, were observed in the hepatocytes of the other chimpanzee receiving inoculum A. The second two animals were infected with a different human plasma containing infectious NANB material (inoculum B). Both animals developed mild increased serum enzyme levels that were variable but generally elevated throughout the course of this study (220 days); minor, equivocal histologic changes were also observed. Intranuclear and intracytoplasmic particles, 20 ± 1 nm and 37 nm in diameter, respectively, were visualized in the liver of one of the two chimpanzees infected with inoculum B; intranuclear particles were observed in one of seventy‐five hepatocytes and intracytoplasmic particles were observed less frequently. In this same animal, intracytoplasmic circular membrane fusions, similar, if not identical to those described above, were also noted. The intranuclear particles observed in animals receiving inocula A and B were essentially identical, as were the cytoplasmic membrane fusions. Thus, both inocula produced nuclear and cytoplasmic ultrastructural changes. The intracytoplasmic particle clusters (37 nm) were seen in only one animal and demonstrated a high degree of homogeneity, as evidenced by their presence in highly ordered crystalline arrays. All chimpanzees were screened for and found to be negative for evidence of hepatitis A and B, as well as for Epstein‐Barr virus or cytomegalo‐virus‐induced hepatitis. Previous studies have suggested that nuclear and cytoplasmic ultrastructural changes, similar to those described herein, result from two distinct NANB infectious agents. In contrast, our data suggest that both morphologic changes may be caused by a single agent.