Anti-HBV activity of TRL mediated by recombinant adenovirus

World J Gastroenterol. 2005 May 7;11(17):2574-8. doi: 10.3748/wjg.v11.i17.2574.

Abstract

Aim: To investigate the inhibitive effect of hepatitis B virus (HBV)-TRL on HBV replication.

Methods: Based on previously constructed pcDNA3.1(-)/TRL, TR, TRmut, HBV core protein (HBVc) and hEDN, interest gene sequences TRL, TR, HBVc and hEDN were inserted into adenovirus shuttle plasmid pDC316 respectively and co-transfected HEK293 cells with rescue plasmid pBHGloxdeltaE1,3Cre to acquire RAd/TRL, TR, HBVc and hEDN. And then RAds were identified, amplified and the titers in HEK293 cells were determined. RAd/TRL and TR were named as the experimental groups, and others were control ones. After HepG2.2.15 cells were infected, RAd/TRL expression was identified by indirect immunofluorescence staining. Supernatant HBV-DNA content was determined by fluorescent quantification PCR. Meanwhile, metabolism of HepG2.2.15 cells was evaluated by MTT colorimetry.

Results: RAd vectors with distinct interest gene sequence were successfully constructed. Effective expression of RAd/TRL in HepG2.2.15 cells resulted in a significant decrease of supernatant HBV-DNA content compared to RAd/TR (0.63+/-0.14 vs 1.60+/-0.47, P = 0.0266, <0.05) and other control groups (0.63+/-0.14 vs 8.50+/-2.78, 8.25+/-2.26, 8.25+/-2.29, 8.50+/-1.51, 8.57+/-1.63, P<0.01). MTT assay suggested that there were no significant differences in cell metabolic activity between groups (P>0.05).

Conclusion: The construction and expression of RAd/TRL has been achieved and it could inhibit HBV replication successfully, which has laid the foundation for further research on anti-HBV activity in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Carcinoma, Hepatocellular
  • Cell Line, Tumor
  • Genetic Therapy / methods*
  • Hepatitis B / virology*
  • Hepatitis B virus / genetics*
  • Hepatitis B virus / growth & development*
  • Humans
  • Liver Neoplasms
  • Plasmids / genetics
  • Recombinant Proteins / genetics
  • Virus Replication

Substances

  • Recombinant Proteins