RT Journal Article SR Electronic(1) A1 Tsuge, Masataka A1 Hiraga, Nobuhiko A1 Akiyama, Rie A1 Tanaka, Sachi A1 Matsushita, Miyuki A1 Mitsui, Fukiko A1 Abe, Hiromi A1 Kitamura, Shosuke A1 Hatakeyama, Tsuyoshi A1 Kimura, Takashi A1 Miki, Daiki A1 Mori, Nami A1 Imamura, Michio A1 Takahashi, Shoichi A1 Hayes, C. Nelson A1 Chayama, KazuakiYR 2010 T1 HBx protein is indispensable for development of viraemia in human hepatocyte chimeric mice JF Journal of General Virology, VO 91 IS 7 SP 1854 OP 1864 DO https://doi.org/10.1099/vir.0.019224-0 PB Microbiology Society, SN 1465-2099, AB 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., UL https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.019224-0