%0 Journal Article %A Tsuge, Masataka %A Hiraga, Nobuhiko %A Akiyama, Rie %A Tanaka, Sachi %A Matsushita, Miyuki %A Mitsui, Fukiko %A Abe, Hiromi %A Kitamura, Shosuke %A Hatakeyama, Tsuyoshi %A Kimura, Takashi %A Miki, Daiki %A Mori, Nami %A Imamura, Michio %A Takahashi, Shoichi %A Hayes, C. Nelson %A Chayama, Kazuaki %T HBx protein is indispensable for development of viraemia in human hepatocyte chimeric mice %D 2010 %J Journal of General Virology, %V 91 %N 7 %P 1854-1864 %@ 1465-2099 %R https://doi.org/10.1099/vir.0.019224-0 %I Microbiology Society, %X 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. %U https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.019224-0