期刊
ANTIVIRAL RESEARCH
卷 101, 期 -, 页码 68-74出版社
ELSEVIER
DOI: 10.1016/j.antiviral.2013.10.019
关键词
Hepatitis B virus; Hydrodynamic injection; Animal model; Lentiviral vector; Therapeutic vaccine
资金
- China Mega-projects of Science Research for the RD of New Drugs [2009ZX09102-237]
- China Mega-project for Infectious Diseases of China [2013ZX10004-601]
Establishment of a non-transgenic mouse model of persistent hepatitis B virus (HBV) infection is urgently needed. In this study, we constructed novel lentiviral-transfer plasmids containing HBV replicon DNA (pCS-HBV1.3, containing a 1.3-fold-overlength genome of HBV) and employed hydrodynamic injection (HDI) to develop an HBV-persistent mouse model. We explored the impact of host (different mouse strains, BALB/c and C57BL/6), gender, and the plasmid backbone on persistent HBV in mice. Our data showed that HBV antigenaemia (HBsAg, HBeAg) and HBV DNA persisted for >56 days post-injection, while the appearance of anti-HBs antibody in the serum was only found among <30% of female C57BL/6 mice injected with pCS-HBV1.3. Moreover, HBcAg and HBV DNA were also detected in the liver of HDI mice. Compared with previous AAV-backbone based HBV replicon DNA transfer, we found that the HDI transfer with the lentiviral vector-based HBV replicon (pCS-HBV1.3) in this study resulted in a significantly higher level of HBV DNA transfer in the liver and longer persistence of HBV DNA and antigenaemia in the serum. Furthermore, we also showed that immunization of HBV replicon transfer mice with the novel HBSS1-based vaccines was able to overcome tolerance against HBV in mice and induces robust immunity (humoral as well as T-cell responses), followed by the clearance of the HBV viremia. We concluded that lentiviral backbone-based transfer vectors more readily establish persistent HBV infection in mouse models via HDI, providing a new tool useful for the study of HBV infection and immune-based therapies. (C) 2013 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据