Experimental infection of chimpanzees with antihemophilic (factor viii) materials: Recovery of virus‐like particles associated with non‐A, non‐B hepatitis

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Abstract
Non‐A, non‐B viral hepatitis was transmitted to four colony‐born chimpanzees by infusion of three lots of antihemophilic factor (factor VIII) implicated in the transmission of non‐A, non‐B hepatitis to two human recipients. All four inoculated animals showed histopathological evidence of viral hepatitis, and all demonstrated significant ALT elevations between three and seven and one‐half weeks after inoculation. Acute‐phase plasma from one of the infected chimpanzees (no. 771) was shown to induce non‐A, non‐B hepatitis in two other chimpanzees approximately three weeks after their inoculation. In addition, an acute‐phase open liver wedge biopsy obtained from animal no. 771 was processed and examined by immune electron microscopy (IEM) for virus‐like particles with convalescent serum from a serologically confirmed case of non‐A, non‐B hepatitis. Twenty‐five to 30 nm (mean = 27 nm) diameter viruslike particles that were either “full” or “empty” were identified in this liver preparation by IEM. Two additional chimpanzees inoculated with a cesium chloride gradient fraction of an isopycnically banded liver homogenate (animal no. no. 771) also developed elevated ALT activity two to two and one‐half weeks later. Our findings have experimentally verified that commercially produced factor VIII materials can induce non‐A, non‐B hepatitis in chimpanzees and that the disease can be subpassaged in these animals by inoculation of either acute‐phase plasma or liver. These results also provide evidence for the association of 27 nm‐diameter virus‐like particles with non‐A, non‐B viral hepatitis.