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Recombinant lentivirus-delivered short hairpin RNAs targeted to conserved coxsackievirus sequences protect against viral myocarditis and improve survival rate in an animal model

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Abstract

Coxsackieviruses are important human pathogens that induce myocarditis and pancreatitis. However, there are no vaccines or therapeutic reagents for their clinical treatment. Although RNA interference (RNAi)-based approaches to the prevention of viral production have been developed recently, limitations to the in vivo delivery systems and variations in the viral target sequences still hamper the strategy. In this study, to overcome these limitations, we have constructed recombinant lentivirus-delivered short hairpin RNAs (shRNAs) against sequences in highly conserved cis-acting replication element (CRE) within the 2C protein of coxsackievirus B3 (CVB3), designated MET-2C. A recombinant lentivirus, designated Met-2C lenti, was constructed that contains the MET-2C sequence, which acts as a shRNA. Met-2C lenti clearly reduced viral production in CVB3-infected cells in vitro. Moreover, the mice injected intraperitoneally with Met-2C lenti had significant reductions in viral titers, viral myocarditis, and proinflammatory cytokines after challenge with CVB3, compared with those in GFP lenti infected control mice. Moreover, Met-2C lenti improved survival rate compared with that of the GFP lenti infected control group. Therefore, Met-2C lenti is potentially a clinical therapeutic agent for the treatment of viral myocarditis.

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References

  1. H.T. Aretz, M.E. Billingham, W.D. Edwards, S.M. Factor, J.T. Fallon, J.J. Fenoglio, E.G. Olsen, F.J. Schoen, Am. J. Cardiovasc. Pathol. 1, 3 (1987)

    PubMed  CAS  Google Scholar 

  2. T.A. Manolio, K.L. Baughman, R. Rodeheffer, T.A. Pearson, J.D. Bristow, V.V. Michels, W.H. Abelmann, W.R. Harlan, Am. J. Cardiol. 69, 1458 (1992)

    Article  PubMed  CAS  Google Scholar 

  3. K. Klingel, M. Sauter, C.T. Bock, G. Szalay, J.J. Schnorr, R. Kandolf, Med. Microbiol. Immunol. 193, 101 (2004)

    Google Scholar 

  4. B. Maisch, A.D. Ristic, G. Hufnagel, S. Pankuweit, Cardiovasc. Pathol. 11, 112 (2002)

    Article  PubMed  CAS  Google Scholar 

  5. J.Y. Kim, E.S. Jeon, B.K. Lim, S.M. Kim, S.K. Chung, J.M. Kim, S.I. Park, I. Jo, J.H. Nam, Vaccine 23, 1672 (2005)

    Article  PubMed  CAS  Google Scholar 

  6. A. Henke, R. Zell, A. Stelzner, Antiviral Res. 49, 49 (2001)

    Article  PubMed  CAS  Google Scholar 

  7. N. Manjunath, P. Kumar, S.K. Lee, P. Shankar, Trends Immunol. 27, 328 (2006)

    Article  PubMed  CAS  Google Scholar 

  8. G. Meister, T. Tuschl, Nature 431, 343 (2004)

    Google Scholar 

  9. G.J. Hannon, J.J. Rossi, Nature 431, 371 (2004)

    Google Scholar 

  10. R. Zufferey, T. Dull, R.J. Mandel, A. Bukovsky, D. Quiroz, L. Naldini, D. Trono D, J. Virol. 72, 9873 (1998)

    PubMed  CAS  Google Scholar 

  11. K.V. Morris, J.J. Rossi, Gene Ther. 13, 553 (2006)

    Article  PubMed  CAS  Google Scholar 

  12. D.A. Rubinson, C.P. Dillon, A.V. Kwiatkowski, C. Sievers, L. Yang, J. Kopinja, D.L. Rooney, M.M. Ihrig, M.T. McManus, F.B. Gertler, M.L. Scott, L. Van Parijs, Nat. Genet. 33, 401 (2003)

    Article  PubMed  CAS  Google Scholar 

  13. R.G. Meyer, M.L. Meyer-Ficca, H. Kaiser, H. Kaiser, H.C. Selinka, R. Kandolf, J.H. Kupper, Virus Res. 104, 17 (2004)

    Article  PubMed  CAS  Google Scholar 

  14. K.U. Knowlton, E.S. Jeon, N. Berkley, R. Wessely, S. Huber, J. Virol. 70, 7811 (1996)

    PubMed  CAS  Google Scholar 

  15. H.S. Lee, J. Ahn, Y. Jee, I.S. Seo, E.J. Jeon, E.S. Jeon, C.H. Joo, Y.K. Kim, H. Lee, J. Gen. Virol. 88, 2003 (2007)

    Article  PubMed  CAS  Google Scholar 

  16. Y. Seko, N. Takahashi, H. Yagita, K. Okumura, Y. Yazaki, J. Pathol. 183, 105 (1997)

    Article  PubMed  CAS  Google Scholar 

  17. S. Schubert, H.P. Grunert, H. Zeichhardt, D. Werk, V.A. Erdmann, J. Kurreck, J. Mol. Biol. 346, 457 (2005)

    Article  PubMed  CAS  Google Scholar 

  18. S. Schubert, H.P. Grunert, H. Zeichhardt, D. Werk, V.A. Erdmann, J. Kurreck, J. Mol. Biol. 346, 457 (2005)

    Article  PubMed  CAS  Google Scholar 

  19. J. Yuan, P.K. Cheung, H.M. Zhang, D. Chau, D. Yang, J. Virol. 79, 2151 (2005)

    Article  PubMed  CAS  Google Scholar 

  20. J. Ahn, E.S. Jun, H.S. Lee, S.Y. Yoon, D. Kim, C.H. Joo, Y.K. Kim, H. Lee, J. Virol. 79, 8620 (2005)

    Article  PubMed  CAS  Google Scholar 

  21. D. Werk, S. Schubert, V. Lindig, H.P. Grunert, H. Zeichhardt, V.A. Erdmann, J. Kurreck, Biol. Chem. 386, 857 (2005)

    Article  PubMed  CAS  Google Scholar 

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Acknowledgement

This work was supported by grant no. R01-2005-000-10668-0 from the Basic Research Program of the Korea Science and Engineering Foundation.

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Author notes

  1. Jae-Hwan Nam

    Present address: Department of Biotechnology, The Catholic University of Korea, 43-1, Yeokgok 2-dong, Wonmi-gu, Bucheon-si, Gyeonggi-do, 420-743, Korea

Authors and Affiliations

  1. Department of Biotechnology, The Catholic University of Korea, 43-1, Yeokgok 2-dong, Wonmi-gu, Bucheon-si, Gyeonggi-do, 420-743, Korea

    Yeon-Jung Kim, Soo-Young Jeung, Dae-Sun Kim, Ha-Na Na & Young-Joo Cho

  2. Research Institute for Macromolecules, University of Ulsan College of Medicine, P.O. Box 145, Seoul, Korea

    Jeonghyun Ahn & Heuiran Lee

  3. Department of Internal Medicine, Sungkynkwan University School of Medicine, Seoul, 135-710, Korea

    Soo-Hyeon Yun & Eun-Seok Jeon

  4. Department of Virology, Division of Enteric and Hepatitis Viruses, National Institute of Health, Seoul, 122-701, Korea

    Youngmee Jee

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  1. Yeon-Jung Kim
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Correspondence to Jae-Hwan Nam.

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Kim, YJ., Ahn, J., Jeung, SY. et al. Recombinant lentivirus-delivered short hairpin RNAs targeted to conserved coxsackievirus sequences protect against viral myocarditis and improve survival rate in an animal model. Virus Genes 36, 141–146 (2008). https://doi.org/10.1007/s11262-007-0192-y

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  • DOI: https://doi.org/10.1007/s11262-007-0192-y

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