Experimental transfection of Macaca sylvanus with cloned human hepatitis B virus

This study evaluated Macaca sylvanus, a small North African monkey, as a potential primate model for hepatitis B virus (HBV) research. Three monkeys were directly inoculated into the liver with replication-competent cloned HBV DNA. Two of three transfected animals developed HBV infection markers, including detectable HBsAg in serum by day 2 post-transfection persisting 4-7 weeks, and HBV DNA detectable by PCR throughout the follow-up period. Serum ultracentrifugation and electron microscopy confirmed the presence of complete 42 nm HBV Dane particles. Both infected animals displayed elevated liver enzymes (ALT/AST) and histological evidence of acute hepatitis with hepatocyte swelling and early periportal fibrosis. HBV DNA replication was confirmed intraheppatically by PCR. Control animals developed no infection markers. The results demonstrate successful HBV replication in M. sylvanus associated with acute hepatitis. The authors conclude this species could provide a valuable new primate model for studying HBV replication and testing antiviral therapeutics and vaccines, particularly if chronic infection can be established through serial passage or immunosuppression.

Key findings

• Two of three M. sylvanus monkeys developed HBV infection after intrahepatic transfection with cloned HBV DNA, showing HBsAg persistence for 4-7 weeks and sustained HBV DNA detection by PCR
• Complete 42 nm HBV Dane particles were identified in infected monkey serum by electron microscopy and sucrose gradient analysis, confirming viral particle production
• Infected monkeys exhibited elevated liver transaminases (ALT/AST) and histological evidence of acute hepatitis including hepatocyte swelling and early fibrosis, absent in controls
• M. sylvanus represents a potentially useful new primate model for HBV research that is more accessible than endangered chimpanzees and showed superior HBV marker persistence compared to other experimental models like tupaias