title: Antiviral resistance mutations potentiate HBV surface antigen-induced transcription of hfgl2 prothrombinase gene.
abstract: 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.
authors.affiliation: Department and Institute of Infectious Disease, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Weina
authors.initials: W
authors.lastname: Li
authors.forename: Meifang
authors.initials: M
authors.lastname: Han
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: Dan
authors.initials: D
authors.lastname: Chen
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Luo
authors.forename: Qin
authors.initials: Q
authors.lastname: Ning
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D001483:Base Sequence; D002460:Cell Line; D024921:Drug Resistance, Multiple, Viral; D005340:Fibrinogen / Q000235:genetics* / Q000378:metabolism; D006509:Hepatitis B / Q000201:enzymology* / Q000235:genetics / Q000821:virology; D006514:Hepatitis B Surface Antigens / Q000235:genetics* / Q000378:metabolism*; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic; D013925:Thromboplastin / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D000998:Antiviral Agents; C095202:FGL2 protein, human; D006514:Hepatitis B Surface Antigens; D005340:Fibrinogen; D013925:Thromboplastin