ABSTRACT
The hepatitis B virus X (HBX) protein has been implicated in both hepatitis B virus-related pathogenesis and also in diverse cellular processes. The diversity of its activities may be mediated through its interaction with cellular organelles. However no clearly defined subcellular localization of HBX is available. We report here the localization of HBX in the proteasome complexes using green fluorescent protein tag. A new proteasome-targeting domain has also been defined in HBX by deletion study. Furthermore, a functional role of HBX in the cellular processes mediated by the proteasome complexes has been suggested by its cell cycle-independent localization in the proteasome. Further analysis of the functional role of HBX in the proteasome complexes should provide more information on the underlying mechanism of HBX ativities.
Subject(s)
Cysteine Endopeptidases/metabolism , Multienzyme Complexes/metabolism , Trans-Activators/metabolism , Animals , Carcinoma, Hepatocellular , Cell Cycle , Green Fluorescent Proteins , Humans , Luminescent Proteins/genetics , Luminescent Proteins/metabolism , Mammals , Proteasome Endopeptidase Complex , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Sequence Deletion , Trans-Activators/genetics , Tumor Cells, Cultured , Viral Regulatory and Accessory ProteinsABSTRACT
OBJECTIVES: To provide intra-familial evidence on the horizontal transmission of hepatitis B virus surface antigen (HBsAg) mutant G145R. METHODS: Serum samples from family members of 10 vaccinated infants who carried this G145R mutant were collected. The presence of the mutant was analysed by polymerase chain reaction (PCR) and sequencing. RESULTS: The G145R mutant was identified in family members of three of the 10 infants. In family 1, the mutant found initially in child 1 was identified in another child and the father. In families 2 and 3, the G145R mutant detected previously in child 1 was detected in the father. Additional mutations in HBsAg were identified in at least two members in family 1 and 2, suggesting horizontal transmission of the mutant among them. The G145R mutant was found in samples with high levels of neutralizing antibody against HBV (anti-HBs). In addition, liver damage was seen in one G145R carrier infant. CONCLUSIONS: The G145R mutant could be transmitted horizontally among family members, and this could occur in the presence of high levels of anti-HBs. Improvement of detection system for the G145R and other HBsAg mutant will be needed for their effective control.
