Effects of naturally occurring mutations in hepatitis B virus core promoter on transcriptional activity

Hepatitis B virus (HBV) with mutations in the core promoter is thought to b e selected naturally during chronic infection. In this study, effects of na turally occurring mutations in the HBV core promoter on transcriptional act ivity are anlayzed. To evaluate whether mutations in the core promoter affe ct transcriptional activity, chloramphenicol acetyltransferase (CAT) assay was performed. When CAT plasmids were transfected into human hepatoma cells , the double mutation (A to T at nucleotide (nt) 1762 and G to A at nt 1764 ) resulted in increased core promoter activity and an additional mutation ( T to C at nt 1753) further enhanced the transcriptional activity. In the ge l mobility shift assay, the double mutation and a T-to-C mutation altered t he protein binding to the corresponding element. The results suggest that a T-to-C mutation at nt 1753, in addition to the double mutation, significan tly influences the HBV core promoter activity. (C) 2000 Elsevier Science Ir eland Ltd. All rights reserved.