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Int. J. Mol. Sci. 2015, 16(3), 5141-5160; doi:10.3390/ijms16035141

The Infection Efficiency and Replication Ability of Circularized HBV DNA Optimized the Linear HBV DNA in Vitro and in Vivo

1
Laboratory of Molecular Biology on Infectious Diseases and Institute for Viral Hepatitis, Ministry of Education, Chongqing Medical University, Chongqing 400016, China
2
Laboratory Animal Center, Chongqing Medical University, Chongqing 400016, China
*
Author to whom correspondence should be addressed.
Academic Editor: William Chi-shing Cho
Received: 30 November 2014 / Revised: 19 January 2015 / Accepted: 17 February 2015 / Published: 5 March 2015
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

Studies on molecular mechanisms of the persist infection of hepatitis B virus have been hampered by a lack of a robust animal model. We successfully established a simple, versatile, and reproducible HBV persist infection model in vitro and in vivo with the circularized HBV DNA. The cells and mice were transfected or injected with circularized HBV DNA and pAAV/HBV1.2, respectively. At the indicated time, the cells, supernatants, serum samples, and liver tissues were collected for virological and serological detection. Both in vitro and in vivo, the circularized HBV DNA and pAAV/HBV1.2 could replicate and transcribe efficiently, but the infection effect of the former was superior to the latter (p < 0.05). The injection of circularized HBV genome DNA into the mice robustly supported HBV infection and approximately 80% of HBV infected mice established persistent infection for at least 10 weeks. This study demonstrated that the infection efficiency and replication ability of the circularized structure of HBV DNA overmatched that of the expression plasmid containing the linear structure of HBV DNA in vitro and in vivo. Meanwhile, this research results could provide useful tools and methodology for further study of pathogenic mechanisms and potential antiviral treatments of human chronic HBV infection in vitro and in vivo. View Full-Text
Keywords: hepatitis B virus (HBV); circularized HBV DNA; covalently closed circular DNA (cccDNA); hepatocellular carcinoma (HCC); persistent infection; viral replication hepatitis B virus (HBV); circularized HBV DNA; covalently closed circular DNA (cccDNA); hepatocellular carcinoma (HCC); persistent infection; viral replication
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Figure 1a

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Li, X.; Zhu, J.; Lai, G.; Yan, L.; Hu, J.; Chen, J.; Tang, N.; Huang, A. The Infection Efficiency and Replication Ability of Circularized HBV DNA Optimized the Linear HBV DNA in Vitro and in Vivo. Int. J. Mol. Sci. 2015, 16, 5141-5160.

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