Molecular characterization, evolution and cross-species transmission study in severe combined immunodeficiency transgenic mice with human hepatocytes of gibbon and orangutan hepatitis B virus

Abstract

Hepatitis B virus does not only exclusively infect humans, but also can be found in non-human primates. The genome organization of non-human primate HBV is nearly identical to that human HBV. There are the data on cross-species transmission of human HBVs to the non-human primates. However, a cross-species transmission of HBVs from non-human primates to human has not been yet been elucidated. One hundred and four non-human primates comprising 12 species were subjected to screen for the serological HBsAg, anti-HBs and anti-HBc markers. Subsequently, HBV DNA detection, whole genome characterization, phylogenetic analysis and evolution study were evaluated and analyzed. The cross-species transmission study in severe combined immunodeficiency (SCID) mice with human hepatocytes was performed. HBV infection was detected in gibbon (5/25) and orangutan (7/54). Phylogenetic analysis was performed and analyzed. The gibbon and orangutan viruses clustered within their respective groups. Evolutionary study revealed that the population growth rate of non-human primate HBV started a rapid increase in the effective population size around year 1750 to 1850. GiHBV was occurred before OuHBV and has evolutionary rate approximately 10[superscript -4] subs/site/year. OuHBV and GiHBV can replicate in chimeric SCID mice with human hepatocytes. The results showed indirect evidence of cross-species transmission of non-human primate to human could be occurred.