Biochemistry (Moscow)

, 76:1043 | Cite as

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

  • Weina Li
  • Meifang Han
  • Yong Li
  • Dan Chen
  • Xiaoping Luo
  • Qin Ning
Article
  • 81 Downloads

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.

Key words

hfgl2 antiviral resistance HBsAg transcription mutation 

Abbreviations

fgl2

fibrinogen-like protein 2

HBc

hepatitis B virus core protein

HBs

hepatitis B virus S protein

HBsAg

HBV surface antigen

HBV

hepatitis B virus

HBx

hepatitis B virus X protein

NA

nucleoside(tide) analogs

RT

reverse transcriptase

YMDD

tyrosine-methionine-aspartate-aspartate

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Copyright information

© Pleiades Publishing, Ltd. 2011

Authors and Affiliations

  • Weina Li
    • 1
  • Meifang Han
    • 1
  • Yong Li
    • 1
  • Dan Chen
    • 1
  • Xiaoping Luo
    • 2
  • Qin Ning
    • 1
  1. 1.Department and Institute of Infectious Disease, Tongji Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
  2. 2.Department of Pediatrics, Tongji Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

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