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Successful establishment and evaluation of a new animal model for studying the hepatitis B virus YVDD mutant

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Abstract

The treatment of infection with lamivudine-resistant mutants of hepatitis B virus (HBV) with mutations in the YMDD motif has become a crucial issue in the clinic. In this work, the plasmids pcDNA3.1 (+)-HBV/C-YVDD and pcDNA3.1 (+)-HBV/C-YMDD were constructed and injected into BALB/c mice using a hydrodynamics-based procedure to investigate viral replication and expression of HBV lamivudine-resistant YVDD mutants in vivo. Compared with the YMDD group, HBsAg levels were higher in sera of mice in the YVDD group, but HBeAg levels were lower on day 1 after injection. Levels of HBcAg in hepatocytes were higher in the YVDD group on day 1, whereas the HBsAg levels were lower. The levels of HBV mRNA in the liver were higher in mice in the YVDD group on day 1 after injection. The results showed that injection with these plasmids resulted in efficient initiation of replication of HBV in mice and also suggested that the combined mutations in YVDD mutants could affect the replication process.

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Acknowledgments

This work was supported by National Natural Science Foundation of China, (Grant No. 31100077), China Postdoctoral Science Foundation Funded Project (Grant No. 2012M510987), Scientific Research Foundation of Health Committee, Heilongjiang, China (No. 2011-207) and a grant from Science and Technology Research Project of Educational Committee, Heilongjiang, China (No. 12511179).

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Authors and Affiliations

  1. Department of Microbiology, The Heilongjiang Key Laboratory of Immunity and Infection, Pathogenic Biology, Harbin Medical University, 157 Baojian Road, Nangang, Harbin, Heilongjing, 150081, China

    Yan-Xiu Ma, Zhi-Wei Song, Xu Teng, Li-Juan Fu, Mei-Li Hao, Si-Jia Chen, Wei-Zhen Xu & Hong-Xi Gu

  2. Laboratory Diagnosis Department, The First Affiliated Hospital of Harbin Medical University, 199 Xidazhi Street Nangang, Harbin, 150001, China

    Zhi-Wei Song

  3. Department of Infectious Diseases, Heilongjiang Province Hospital, 82 Zhongshan Road, Xiangfang, Harbin, 150001, China

    Li-Juan Fu

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  1. Yan-Xiu Ma
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  2. Zhi-Wei Song
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  3. Xu Teng
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  4. Li-Juan Fu
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  5. Mei-Li Hao
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  7. Wei-Zhen Xu
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  8. Hong-Xi Gu
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Correspondence to Hong-Xi Gu.

Additional information

Y.-X. Ma, Z.-W. Song and X. Teng contributed equally in this study.

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Ma, YX., Song, ZW., Teng, X. et al. Successful establishment and evaluation of a new animal model for studying the hepatitis B virus YVDD mutant. Arch Virol 158, 785–791 (2013). https://doi.org/10.1007/s00705-012-1550-1

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  • DOI: https://doi.org/10.1007/s00705-012-1550-1

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