Antiviral resistance mutations potentiate HBV surface antigen-induced transcription of hfgl2 prothrombinase gene

• Published in: Biochemistry (Moscow) Vol. 76; no. 9; pp. 1043 - 1050
• Main Authors: Li, Weina, Han, Meifang, Li, Yong, Chen, Dan, Luo, Xiaoping, Ning, Qin
• Format: Journal Article
• Language: English
• Published: Dordrecht SP MAIK Nauka/Interperiodica 01.09.2011; Springer; Springer Nature B.V
• Subjects: Animals; Antigens; Antiviral agents; Antiviral Agents - pharmacology; Base Sequence; Biochemistry; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Cell Line; Development and progression; Drug resistance; Drug Resistance, Multiple, Viral; Fibrinogen - genetics; Fibrinogen - metabolism; Genetic aspects; Genetic transcription; Genomics; Hepatitis; Hepatitis B; Hepatitis B - enzymology; Hepatitis B - genetics; Hepatitis B - virology; Hepatitis B Surface Antigens - genetics; Hepatitis B Surface Antigens - metabolism; Hepatitis B virus - drug effects; Hepatitis B virus - genetics; Hepatitis B virus - metabolism; Humans; Life Sciences; Liver diseases; Microbiology; Molecular Sequence Data; Mutation; Promoter Regions, Genetic; Proteins; Thromboplastin - genetics; Thromboplastin - metabolism; Transcription, Genetic; Virology; mutation; HBsAg; antiviral resistance; transcription
• ISSN: 0006-2979; 1608-3040
• DOI: 10.1134/S0006297911090094

Antiviral resistance mutations in the hepatitis B virus (HBV) polymerase ( pol ) gene have been demonstrated to play an important role in the progression of liver disease and the development of hepatocellular carcinoma. The HBV pol gene overlaps the S gene encoding surface antigen (HBsAg). Previous studies from our laboratory have shown that HBV core protein (HBc) and X protein (HBx), but not HBV S protein (HBs), promote hfgl2 prothrombinase transcription. To investigate whether the nucleotide (nucleoside)-induced resistant mutations of HBs potentiate transcription of hfgl2 prothrombinase gene, we generated two mutant HB expression constructs harboring rtM204V/sI195M or rtM204I/sW196L mutations. Two mutant expression plasmids were co-transfected with hfgl2 promoter luciferase-reporter plasmids and β-galactosidase plasmid in CHO cells and HepG2 cells, respectively. Luciferase assay showed that the rtM204I/V mutant HBs could activate the transcription of hfgl2 promoter compared with the wild type HBs. Site-directed mutagenesis and further experiment (co-transfection) demonstrated that transcription factor Ets translocated to its cognate cis -element in the hfgl2 promoter. The results show that mutated HBs caused by antiviral drug resistance induce transcription of the hfgl2 gene dependent on the transcription factor Ets.