Basic Research
Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Jun 28, 2008; 14(24): 3849-3854
Published online Jun 28, 2008. doi: 10.3748/wjg.14.3849
Combination of small interfering RNAs mediates greater suppression on hepatitis B virus cccDNA in HepG2.2.15 cells
Xiao-Min Xin, Gui-Qiu Li, Ying-Yu Jin, Min Zhuang, Di Li
Xiao-Min Xin, Gui-Qiu Li, Ying-Yu Jin, Department of Laboratory Diagnosis, the First Affiliated Hospital of Harbin Medical University, Harbin 150081, Heilongjiang Province, China
Min Zhuang, Di Li, Department of Microbiology, Harbin Medical University, Harbin 150081, Heilongjiang Province, China
Author contributions: Xin XM and Li GQ contributed equally to this work; Xin XM, Li GQ designed and performed the research; Jin YY, Li D, Zhuang M analyzed the data.
Correspondence to: Di Li, Department of Microbiology, Harbin Medical University, Harbin 150081, Heilongjiang Province, China. lgq7566@126.com
Telephone: +86-451-86685722
Fax: +86-451-86685722
Received: January 29, 2008
Revised: May 19, 2008
Accepted: May 26, 2008
Published online: June 28, 2008
Abstract

AIM: To observe the inhibition of hepatitis B virus (HBV) replication and expression in HepG2.2.15 cells by combination of small interfering RNAs (siRNAs).

METHODS: Recombinant plasmid psil-HBV was constructed and transfected into HepG2.2.15 cells. At 48 h, 72 h and 96 h after transfection, culture media were collected and cells were harvested for HBV replication assay. HBsAg and HBeAg in the cell culture medium were detected by enzyme-linked immunoadsorbent assay (ELISA). Intracellular viral DNA and covalently closed circular DNA (cccDNA) were quantified by real-time polymerase chain reaction (PCR). HBV viral mRNA was reverse transcribed and quantified by reverse-transcript PCR (RT-PCR).

RESULTS: siRNAs showed marked anti-HBV effects. siRNAs could specifically inhibit the expression of HBsAg and the replication of HBV DNA in a dose-dependent manner. Furthermore, combination of siRNAs, compared with individual use of each siRNA, exerted a stronger inhibition on antigen expression and viral replication. More importantly, combination of siRNAs significantly suppressed HBV cccDNA amplification.

CONCLUSION: Combination of siRNAs mediates a stronger inhibition on viral replication and antigen expression in HepG2.2.15 cells, especially on cccDNA amplification.

Keywords: Combination of small interfering RNAs, Covalently closed circular DNA, Hepatitis B virus, RNA interference, HepG2.2.15 cells