Collective repression of the hepatitis B virus enhancer II by human TR4 and TR2 orphan receptors.
OBJECTIVE
The human testicular receptor 4 and 2 (TR4 and TR2) orphan receptors are members of the nuclear receptor superfamily that regulate target gene expression via binding to the consensus AGGTCA direct repeats of the hormone response elements. Previous studies have reported that TR4 and other nuclear receptors could bind to the direct repeat 1 element of the hepatitis B virus (HBV) core promoter.


METHODS
Differential gene expression of HBV caused by TR4 and TR2 was determined by gel retardation and functional assays.


RESULTS
Electrophoretic mobility shift assay demonstrated that TR4 and TR2 might bind to the direct repeat 6 element of the HBV enhancer II region. RESULTS of the dual-luciferasereporter gene assay showed that TR4 and TR2 might significantly suppress HBV gene expression through this direct repeat 6 element in the enhancer II.


CONCLUSIONS
These results implied that TR4 together with its heterodimer partner TR2 could collectively play a significant role in the transcriptional suppression of HBV gene expression via the direct repeat 6 element in the enhancer II. Therefore, the application of nuclear receptors potentially may be antiviral agents in chronic HBV infection.
Lin
Tzu-Jon
TJ
Department of Life Science, National Dong Hwa University, Hualien, Taiwan.
Yang
Ren-You
RY
Lee
Han-Jung
HJ