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Construction of mTNFR1shRNA plasmid and its biological effects on MHV-3 induced fulminant hepatitis in BALB/cJ mice

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Virologica Sinica

Abstract

Previous study on TNFR1-mediated hepatocyte apoptosis has been implicated in the development of fulminant viral hepatitis. To interfere with the potentially effective target, plasmid named p-mTNFR1shRNA complimentary to the sequence responsible for mTNFR1 was also constructed and further confirmed by sequence analysis. To investigate the effect of mTNFR1shRNA plasmid on mTNFR1 expression in vivo and the disease progress in MHV-3 induced fulminant hepatitis mice model. By hydrodynamic injection of mTNFR1shRNA plasmid, the survival rate of mice, hepatic pathological change were examined and compared between mice with/without mTNFR1shRNA plasmid intervention. The expression of mTNFR1 was detected by Real-time PCR, immunohistochemistry staining. The mTNFR1shRNA plasmid significantly reduced mTNFR1 expression in vivo, markedly ameliorates inflammatory infiltration, prolonged the survival time period and elevated the survival rate from 0 up to 13.3% in Balb/cJ mice with MHV-3 induced fulminant hepatitis. This study was designed to explore the opportunity of RNA interference technique in inhibiting TNFR1 expression, which has been reported to be involved in the development of a variety of diseases including fulminant viral hepatitis and severe chronic hepatitis B.

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Authors and Affiliations

  1. Laboratory of Infectious Immunology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Sui Gao, Ming Wang, Jian-wen Guo, Dong Xi, Xiao-ping Luo & Qin Ning

Authors
  1. Sui Gao
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  2. Ming Wang
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  3. Jian-wen Guo
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  4. Dong Xi
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  5. Xiao-ping Luo
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  6. Qin Ning
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Corresponding author

Correspondence to Qin Ning.

Additional information

Foundation items: National Science Fund of China (NSFC) (30571643, 30672380, 30700702); National Key Basic Research Program of China (2005CB522901, 2007CB 512900).

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Gao, S., Wang, M., Guo, Jw. et al. Construction of mTNFR1shRNA plasmid and its biological effects on MHV-3 induced fulminant hepatitis in BALB/cJ mice. Virol. Sin. 25, 52–58 (2010). https://doi.org/10.1007/s12250-010-3072-x

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  • DOI: https://doi.org/10.1007/s12250-010-3072-x

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