Hepatitis B Virus X Protein Induces Transcription Of Human Potassium Channel Tetramerisation Domain Containing9Gene

Hepatitis B virus is the predominate cause leading to severe hepatitis with a badprognosis in our country (about70%).The pathogenesis of HBV-induced severe hepatitis isvery complicated.The present studies indicate that the activation or control of developmentof severe hepatitis is influenced by viral factors,such as genetype,mutation orreplication,and host factors,such as genetic characteristics,mechanism of immuneinjury,apoptosis or necrosis,as well as their interactions.Considering the viral aspect,HBV-encoding proteins are reported to play important roles in the development of manyliver diseases, such as regulating host genes expression and influencing viral replication.The human potassium channel gene KCTD9, belonging to the novel KCTD family,islocated in chromosome8. In our previous work,human whole genomic gene chip wasadopted to analyze the disparate gene expression in PBMC from patients with severehepatitis B(SHB) or mild chronic hepatitis B(CHB).We found that the expression level ofKCTD9mRNA in SHB was much higher than that in CHB.To explore the viral and host factors which involved in the human KCTD9(hKCTD9)transcription.Eukaryotic expression plasmids of HBc, HBs or HBx were cotransfected withan hKCTD9luciferase report construct into CHO cells respectively. The result of luciferase assay showed that neither HBx protein, significantly enhanced transcription activity ofhKCTD9promoter in CHO cells， wheras neither HBs nor HBc protein displayedtranscription activity on hKCTD9. The transcriptional activity was determined by therelative activity of luciferase and β-galactosidase plasmid served as an internal control.Compared with the control group, relative luciferase activity in CHO cells transfected withpcDNA-HBx was at an average of4.5-fold elevation. These results indicate that HBxprotein activates the hKCTD9gene transcription, wheras HBs and HBc show no effect.Our studies suggest that a strong regulatory region which be responsible for activationof HBx protein on hKCTD9gene transcription was located on-751to-657(relative to thetranscriptional starting site),where there are probably some important cis-elements.