Experimental infection of chimpanzees with antihemophilic (factor VIII) materials: recovery of virus-like particles associated with non-A, non-B hepatitis

J Med Virol. 1979;3(4):253-69. doi: 10.1002/jmv.1890030403.

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 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.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Alanine Transaminase / blood
  • Animals
  • Factor VIII / adverse effects*
  • Female
  • Hepatitis Viruses / isolation & purification*
  • Hepatitis Viruses / ultrastructure
  • Hepatitis, Viral, Human / enzymology
  • Hepatitis, Viral, Human / microbiology
  • Hepatitis, Viral, Human / transmission
  • Humans
  • Liver / microbiology
  • Male
  • Pan troglodytes

Substances

  • Factor VIII
  • Alanine Transaminase