Experimental infection of chimpanzees with antihemophilic (factor VIII) materials: recovery of virus-like particles associated with non-A, non-B hepatitis.
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 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 virus-like 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. 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 champanzees 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.
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D005169:Factor VIII / Q000009:adverse effects*; D005260:Female; D006518:Hepatitis Viruses / Q000302:isolation & purification* / Q000648:ultrastructure; D006525:Hepatitis, Viral, Human / Q000201:enzymology / Q000382:microbiology / Q000635:transmission; D006801:Humans; D008099:Liver / Q000382:microbiology; D008297:Male; D002679:Pan troglodytes
D005169:Factor VIII; D000410:Alanine Transaminase