Serum samples from 4 of the 15 HBV DNA–positive baboons, for which additional serum was available, were tested and found to be negative for HBsAg and anti-HBc. Alanine and aspartate aminotransferase levels were within reference ranges, and after high-speed centrifugation and treatment with antibody against HBsAg, no viral particles were observed in the serum by electron microscopy. Histologic examination of liver tissue from 1 of these baboons (9732) showed mild focal lobular hepatitis but no evidence of interface hepatitis, bridging necrosis, dysplasia of hepatocytes, cirrhosis, or hepatocellular carcinoma (Figure 2, panel A). Immunohistochemical staining of liver tissue showed HBcAg in nuclei of some hepatocytes with a patchy distribution (Figure 2, panel B). HBsAg and 42-nm enveloped (Dane) particles were not detected in the cytoplasm.
Amplification, Sequencing, and Phylogenetic Analysis of HBV Genome from Baboon Liver
The low viral loads indicated that the complete HBV genome could only be amplified subgenomically and because of the small volumes of serum available, liver tissue obtained from baboon 9732 was used to further characterize HBV in baboons. The complete HBV genome was amplified by nested PCR of 8 overlapping subgenomic fragments (Figure 1).