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HBx protein is indispensable for development of viraemia in human hepatocyte chimeric mice

2010; Microbiology Society; Volume: 91; Issue: 7 Linguagem: Inglês

10.1099/vir.0.019224-0

1465-2099

Masataka Tsuge, Nobuhiko Hiraga, R. Akiyama, Sachi Tanaka, Miyuki Matsushita, Fukiko Mitsui, Hiromi Abe, Shigeyuki Kitamura, Tsuyoshi Hatakeyama, T. Kimura, Daiki Miki, Nobuyoshi Mori, Michio Imamura, Shoichi Takahashi, C. Nelson Hayes, Kazuaki Chayama,

Liver Disease Diagnosis and Treatment

The non-structural X protein, HBx, of hepatitis B virus (HBV) is assumed to play an important role in HBV replication. Woodchuck hepatitis virus X protein is indispensable for virus replication, but the duck hepatitis B virus X protein is not. In this study, we investigated whether the HBx protein is indispensable for HBV replication in vivo using human hepatocyte chimeric mice. HBx-deficient (HBx-def) HBV was generated in HepG2 cells by transfection with an overlength HBV genome. Human hepatocyte chimeric mice were infected with HBx-def HBV with or without hepatic HBx expression by hydrodynamic injection of HBx expression plasmids. Serum virus levels and HBV sequences were determined with mice sera. The generated HBx-def HBV peaked in the sucrose density gradient at points equivalent to the generated HBV wild type and the virus in a patient's serum. HBx-def HBV-injected mice developed measurable viraemia only in continuously HBx-expressed liver. HBV DNA in the mouse serum increased up to 9 log10 copies ml−1 and the viraemia persisted for more than 2 months. Strikingly, all revertant viruses had nucleotide substitutions that enabled the virus to produce the HBx protein. It was concluded that the HBx protein is indispensable for HBV replication and could be a target for antiviral therapy.