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小鼠白细胞介素-21基因重组腺病毒可控制慢性HBV感染

高雪萍 周扬 郑新春 易璇 唐利波 侯金林 李咏茵

南方医科大学学报2017,Vol.37Issue(11):1436-1441,6.
南方医科大学学报2017,Vol.37Issue(11):1436-1441,6.DOI:10.3969/j.issn.1673-4254.2017.11.02

小鼠白细胞介素-21基因重组腺病毒可控制慢性HBV感染

A recombinant adenovirus vector carrying murine interleukin-21 gene controls chronic HBV infection in mice

高雪萍 1周扬 1郑新春 1易璇 1唐利波 1侯金林 1李咏茵1

作者信息

  • 1. 器官衰竭防治国家重点实验室//广东省病毒性肝炎研究重点实验室//南方医科大学南方医院感染内科,广东广州 510515
  • 折叠

摘要

Abstract

Objective To investigate the effect of an adenovirus vector containing murine interleukin-21 gene (Ad-GFP-mIL-21) in virus clearance and on the production of HBV-specific antibodies in mice with persistent HBV infection. Methods ELISA and Western blot analysis were used to detect the expression of mIL-21 in the supernatant and cytoplasm of cultured HepG2.2.15 cells after infection by Ad-GFP-mIL-21. Mouse models of chronic HBV infection established by in vivo transduction with rAAV8-1.3HBV were divided into 3 groups for treatment 12 weeks later with injection of Ad-GFP-mIL-21, GFP recombinant adenovirus or PBS via the tail vein. Serum levels of HBsAg, HBsAb, HBcAb, and mIL-21 in the mice were detected using ELISA, and the expression of Ad-GFP-mIL-21 in the organs was observed by fluorescent microscopy at different time points after the injection. Results Ad-GFP-mIL-21 was capable of infecting HepG2.2.15 cells in vitro, and the levels of mIL-21 in the supernatant were correlated with the titers of adenovirus administered and the infection time. In the mice with persistent HBV infection, green fluorescence expression was observed almost exclusively in the liver on day 4 after injection of Ad-GFP-mIL21, and serum levels of IL-21 increased significantly compared with the level before treatment (P<0.05). Although HBsAb was undetectable in both Ad-GFP-mIL21-injected and control mice on day 13, a significantly higher serum level of HBcAb was detected in the mice with Ad-GFP-mIL21 injection (P<0.05). Conclusion Ad-GFP-mIL-21 can efficiently express mIL-21 in mice with chronic HBV infection to downregulate serum levels of HBsAg and promote HBcAb production, suggesting its efficacy in controlling chronic HBV infection.

关键词

乙型肝炎病毒/小鼠白细胞介素-21/重组腺病毒

Key words

hepatitis B virus/murine interleukin-21/recombinant adenovirus

引用本文复制引用

高雪萍,周扬,郑新春,易璇,唐利波,侯金林,李咏茵..小鼠白细胞介素-21基因重组腺病毒可控制慢性HBV感染[J].南方医科大学学报,2017,37(11):1436-1441,6.

基金项目

国家自然科学基金(81671570) Supported by National Natural Science Foundation of China (81671570). (81671570)

南方医科大学学报

OA北大核心CSCDCSTPCDMEDLINE

1673-4254

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