Demonstration of two different types of non-A, non-B hepatitis by reinjection and cross-challenge studies in chimpanzees.

Utilizing immune electron microscopy, viruslike particles were identified in the serums of three apparently healthy, HBsAg-negative blood donors. The serum from one of the donors, when injected into two susceptible chimpanzees, induced non-A, non-B hepatitis with an increase in SGPT level and pathological changes in the liver compatible with acute hepatitis but none of the cytoplasmic ultrastructures previously noted by electron microscopy in non-A, non-B hepatitis. These two chimps did not contract hepatitis when the same inoculum was given again 17 wk after the first injection. When they were subsequently challenged, however, by a chimp inoculum containing viruslike particles known to induce non-A, non-B hepatitis with cytoplasmic tubular ultrastructures, they developed high SGPT levels and these characteristic ultrastructures in their hepatocytes. A third chimp was initially injected with the chimp inoculum containing viruslike particles known to induce hepatitis with tubular ultrastructures, reinjected with the same agent, and then challenged by the human serum containing viruslike particles capable of inducing non-A, non-B hepatitis without tubular ultrastructures. He developed biochemical and pathological evidence of acute hepatitis after the first and the third, but not after the second inoculations. There are at least two kinds of viruslike particles which are associated with infectivity for two different types of non-A, non-B hepatitis; these have been tentatively designated NANB-1 and NANB-2.