title: Hepatitis B virus X protein is not central to the viral life cycle in vitro.
abstract: The hepatitis B x (HBx) gene is the smallest open reading frame of the hepatitis B virus (HBV) genome. It is conserved among all mammalian hepadnaviruses and is expressed during viral infection. While the HBx protein (pX) has been shown to trans-activate the transcription of a wide range of viral and cellular genes and to induce liver cancer in transgenic mice, the significance of pX for the life cycle of HBV itself has not been elucidated. To assess the function of pX in viral replication and virion export, we designed an X-minus mutant by introduction of a stop codon at the beginning of the HBx gene without affecting the viral polymerase gene product. Transient transfection analyses using different cell lines revealed that this X-minus mutant directs the synthesis of wild-type levels of viral proteins, replicative intermediates, and virion export. These data suggest that the expression of the highly conserved HBx gene is not central for the life cycle of HBV in vitro but may be involved in the pathogenicity of hepadnavirus infection, including liver cancer development.
authors.affiliation: Molecular Hepatology Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown 02129.
authors.forename: H E
authors.initials: HE
authors.lastname: Blum
authors.forename: Z S
authors.initials: ZS
authors.lastname: Zhang
authors.forename: E
authors.initials: E
authors.lastname: Galun
authors.forename: F
authors.initials: F
authors.lastname: von Weizsäcker
authors.forename: B
authors.initials: B
authors.lastname: Garner
authors.forename: T J
authors.initials: TJ
authors.lastname: Liang
authors.forename: J R
authors.initials: JR
authors.lastname: Wands
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D016679:Genome, Viral; D006514:Hepatitis B Surface Antigens / Q000235:genetics; D006513:Hepatitis B e Antigens / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D015534:Trans-Activators / Q000235:genetics*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D054334:Viral Regulatory and Accessory Proteins; D014771:Virion / Q000235:genetics / Q000502:physiology; D014779:Virus Replication
chemical_list: D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D015500:Chloramphenicol O-Acetyltransferase