Virus Genes

, Volume 32, Issue 3, pp 299–306 | Cite as

Inhibition of Viruses by RNA Interference

  • Yehuda StramEmail author
  • Larisa Kuzntzova
Review Paper


RNA-mediated interference (RNAi) is a recently discovered process by which dsRNA is able to silence specific gene functions. Although initially described in plants, nematodes and Drosophila, the process is currently considered to be an evolutionarily conserved process that is present in the entire eukaryotic kingdom in which its original function was as a defense mechanism against viruses and foreign nucleic acids. Similarly to the silencing of genes by RNAi, viral functions can be also silenced by the same mechanism, through the introduction of specific dsRNA molecules into cells, where they are targeted to essential genes or directly to the viral genome in case RNA viruses, thus arresting viral replication. Since the pioneering work of Elbashir and coworkers, who identified RNAi activity in mammalian cells, many publications have described the inhibition of viruses belonging to most if not all viral families, by targeting and silencing diverse viral genes as well as cell genes that are essential for virus replication. Moreover, virus expression vectors were developed and used as vehicles with which to deliver siRNAs into cells. This review will describe the use of RNAi to inhibit virus replication directly, as well as through the silencing of the appropriate cell functions.


Viruses RNA interference RNAi Small interfering RNA siRNA 


  1. 1.
    Ingelbrecht, I., Houdt, H., Montagu, M., Depicker, A. 1994Proc. Natl. Acad. Sci. USA911050210506PubMedGoogle Scholar
  2. 2.
    Baulcombe, D.C. 1996Plant Mol. Biol.327988PubMedCrossRefGoogle Scholar
  3. 3.
    Romano, N., Macino, G. 1992Mol. Microbiol.633433353PubMedGoogle Scholar
  4. 4.
    Cogoni, C., Romano, N., Macino, G. 1994Antonie Van Leeuwenhoek65205209PubMedCrossRefGoogle Scholar
  5. 5.
    Zamore, P.D., Tuschl, T., Sharp, P.A., Bartel, D.P. 2000Cell1012533PubMedCrossRefGoogle Scholar
  6. 6.
    Ketting, R.F., Fischer, S.E., Bernstein, E., Sijen, T., Hannon, G.J., Plasterk, R.H. 2001Genes Dev.1526542659PubMedCrossRefGoogle Scholar
  7. 7.
    Bernstein, E., Caudy, A.A., Hammond, S.M., Hannon, G.J. 2001Nature409363366PubMedCrossRefGoogle Scholar
  8. 8.
    Carmell, M.A., Hannon, G.J. 2004Nat. Struct. Mol. Biol.11214218PubMedCrossRefGoogle Scholar
  9. 9.
    G.J. Hannon, P.D. Zamore, in RNAi: A Guide to Gene Silencing, ed. by G.J. Hannon (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 2003) pp 87–108Google Scholar
  10. 10.
    Zhang, H., Kolb, F.A., Jaskiewicz, L., Westhof, E., Filipowicz, W. 2004Cell1185768PubMedCrossRefGoogle Scholar
  11. 11.
    Elbashir, S.M., Lendeckel, W., Tuschl, T. 2001aGenes Dev.15185200CrossRefGoogle Scholar
  12. 12.
    Elbashir, S.M., Martinez, J. 2001bEMBO J.2068776888CrossRefGoogle Scholar
  13. 13.
    Yang, D., Buchholz, F., Huang, Z., Goga, A., Chen, C.Y., Brodsky, F.M., Bishop, J.M. 2002Proc. Natl. Acad. Sci. USA9999429947PubMedCrossRefGoogle Scholar
  14. 14.
    Yang, D., Goga, A., Bishop, J.M. 2004Meth. Mol. Biol.252471482Google Scholar
  15. 15.
    Rand, T.A., Ginalski, K., Grishin, N.V., Wang, X. 2004Proc. Natl. Acad. Sci. USA1011438514389PubMedCrossRefGoogle Scholar
  16. 16.
    Tomari, Y., Matranga, C., Haley, B., Martinez, N., Zamore, P.D. 2004Science30613771380PubMedCrossRefGoogle Scholar
  17. 17.
    Song, J.J., Smith, S.K., Hannon, G.J., Joshua-Tor, L. 2004Science30514341437PubMedCrossRefGoogle Scholar
  18. 18.
    Meister, G., Landthaler, M., Patkaniowska, A., Dorsett, Y., Teng, G., Tuschl, T. 2004Cell15185197Google Scholar
  19. 19.
    Lingel, A., Simon, B., Izaurralde, E., Sattler, M. 2003Nature426465469PubMedCrossRefGoogle Scholar
  20. 20.
    Lingel, A., Simon, B., Izaurralde, E., Sattler, M. 2004Nat. Struct. Mol. Biol.11576577PubMedCrossRefGoogle Scholar
  21. 21.
    Ma, J.B., Ye, K., Patel, D.J. 2004Nature429318322PubMedCrossRefGoogle Scholar
  22. 22.
    Nicholson, R.H., Nicholson, A.W. 2002Genome136773Google Scholar
  23. 23.
    Song, J.J., Smith, S.K., Hannon, G.J., Joshua-Tor, L. 2004Science30514341437PubMedCrossRefGoogle Scholar
  24. 24.
    Song, J.J., Liu, J., Tolia, N.H., Schneiderman, J., Smith, S.K., Martienssen, R.A., Hannon, G.J., Joshua-Tor, L. 2003Nat. Struct. Biol.1010261032PubMedCrossRefGoogle Scholar
  25. 25.
    Parker, J.S., Roe, S.M., Barford, D. 2004EMBO J.2347274737PubMedCrossRefGoogle Scholar
  26. 26.
    Patel, R.C., Sen, G.C. 1994Cell Mol. Biol. Res.40671682PubMedGoogle Scholar
  27. 27.
    Katze, M.G. 1995Trends Microbiol.37578PubMedCrossRefGoogle Scholar
  28. 28.
    Sioud, M., Sorensen, D.R. 2003Biochem. Biophys. Res. Commun.31212201225PubMedCrossRefGoogle Scholar
  29. 29.
    Zhang, X., Shan, P., Jiang, D., Noble, P.W., Abraham, N.G., Kappas, A., Lee, P.J. 2004J. Biol. Chem.2791067710684PubMedCrossRefGoogle Scholar
  30. 30.
    Liu, C., Shi, Y., Han, Z., Pan, Y., Liu, N., Han, S., Chen, Y., Lan, M., Qiao, T., Fan, D. 2003Biochem. Biophys. Res. Commun.312780786PubMedCrossRefGoogle Scholar
  31. 31.
    Futami, T., Miyagishi, M., Seki, M., Taira, K. 2002Nucl. Acids Res. Suppl.2251252Google Scholar
  32. 32.
    Matsukura, S., Jones, P.A., Takai, D. 2003Nucl. Acids Res.31e77PubMedCrossRefGoogle Scholar
  33. 33.
    Wetering, M., Oving, I., Muncan, V., Pon Fong, M.T., Brantjes, H., Leenen, D., Holstege, F.C., Brummelkamp, T.R., Agami, R., Clevers, H. 2003EMBO Rep4609615PubMedCrossRefGoogle Scholar
  34. 34.
    Pinkenburg, O., Platz, J., Beisswenger, C., Vogelmeier, C., Bals, R. 2004J. Virol. Meth.120119122CrossRefGoogle Scholar
  35. 35.
    Sanchez-Vargas, I., Travanty, E.A., Keene, K.M., Franz, A.W., Beaty, B.J., Blair, C.D., Olson, K.E. 2004Virus Res.1026574PubMedCrossRefGoogle Scholar
  36. 36.
    An, D.S., Xie, Y., Mao, S.H., Morizono, K., Kung, S.K., Chen, I.S. 2003Hum. Gene Ther.1412071212PubMedCrossRefGoogle Scholar
  37. 37.
    Lee, J.S., Hmama, Z., Mui, A., Reiner, N.E. 2004J. Biol. Chem.27993799388PubMedCrossRefGoogle Scholar
  38. 38.
    Li, M.J., Rossi, J.J. 2005Meth. Enzymol.392218226PubMedGoogle Scholar
  39. 39.
    Gitlin, L., Karelsky, S., Andino, R. 2002Nature418430434PubMedCrossRefGoogle Scholar
  40. 40.
    Gitlin, L., Stone, J.K., Andino, R. 2005J. Virol.7910271035PubMedCrossRefGoogle Scholar
  41. 41.
    Kahana, R., Kuznetzova, L., Rogel, A., Shemesh, M., Hai, D., Yadin, H., Stram, Y. 2004J. Gen. Virol.8532133217PubMedCrossRefGoogle Scholar
  42. 42.
    Chen, W., Yan, W., Du, Q., Fei, L., Liu, M., Ni, Z., Sheng, Z., Zheng, Z. 2004J. Virol.7869006907PubMedCrossRefGoogle Scholar
  43. 43.
    Rosenberg, S. 2001J. Mol. Biol.313451464PubMedCrossRefGoogle Scholar
  44. 44.
    Thomson, B.J., Finch, R.G. 2005Clin. Microbial Infect.118694CrossRefGoogle Scholar
  45. 45.
    Kronke, J., Kittler, R., Buchholz, F., Windisch, M.P., Pietschmann, T., Bartenschlager, R., Frese, M. 2004J. Virol.17834363446CrossRefGoogle Scholar
  46. 46.
    Yokota, T., Sakamoto, N., Enomoto, N., Tanabe, Y., Miyagishi, M., Maekawa, S., Yi, L., Kurosaki, M., Taira, K., Watanabe, M., Mizusawa, H. 2003EMBO Rep.4602608PubMedCrossRefGoogle Scholar
  47. 47.
    Takigawa, Y., Nagano-Fujii, M., Deng, L., Hidajat, R., Tanaka, M., Mizuta, H., Hotta, H. 2004Microbiol. Immunol.48591598PubMedGoogle Scholar
  48. 48.
    Xu, X., Subbarao, K., Cox, N.J., Guo, Y. 1999Virology2611519PubMedCrossRefGoogle Scholar
  49. 49.
    Class, E.C., Osterhaus, A.D., Beek, R., Jong, J.C., Rimmelzwaan, G.F., Senne, D.A., Krauss, S., Shortridge, K.F., Webster, R.G. 1998Lancet351472477CrossRefGoogle Scholar
  50. 50.
    Guan, Y., Poon, L.L., Cheung, C.Y., Ellis, T.M., Lim, W., Lipatov, A.S., Chan, K.H, Sturm-Ramirez, K.M., Cheung, C.L., Leung, Y.H., Yuen, K.Y., Webster, R.G., Peiris, J.S. 2004Proc. Natl. Acad. Sci. USA10181568161PubMedCrossRefGoogle Scholar
  51. 51.
    Ge, Q., McManus, M.T., Nguyen, T., Shen, C.H., Sharp, P.A., Eisen, H.N., Chen, J. 2003Proc. Natl. Acad. Sci. USA10027182723PubMedCrossRefGoogle Scholar
  52. 52.
    Hui, E.K., Yap, E.M., An, D.S., Chen, I.S., Nayak, D.P. 2004J. Gen. Virol.8518771884PubMedCrossRefGoogle Scholar
  53. 53.
    Ge, Q., Filip, L., Bai, A., Nguyen, T., Eisen, H.N., Chen, J. 2004Proc. Natl. Acad. Sci. USA10186768681PubMedCrossRefGoogle Scholar
  54. 54.
    Tompkins, S.M., Lo, C.Y., Tumpey, T.M., Epstein, S.L. 2004Proc. Natl. Acad. Sci. USA10186828686PubMedCrossRefGoogle Scholar
  55. 55.
    Wang, Z., Ren, L., Zhao, X., Hung, T., Meng, A., Wang, J., Chen, Y.G. 2004J. Virol.7875237527PubMedCrossRefGoogle Scholar
  56. 56.
    Zhang, Y., Li, T., Fu, L., Yu, C., Li, Y., Xu, X., Wang, Y., Ning, H., Zhang, S., Chen, W., Babiuk, L.A., Chang, Z. 2004FEBS Lett.560141146PubMedCrossRefGoogle Scholar
  57. 57.
    Wu, C.J., Huang, H.W., Liu, C.Y., Hong, C.P., Chan, Y.L. 2005Antiviral Res.654548PubMedCrossRefGoogle Scholar
  58. 58.
    Qin, Z.L., Zhao, P., Zhang, X.L., Yu, J.G., Cao, M.M., Zhao, L.J., Luan, J., Qi, Z.T. 2004Biochem. Biophys. Res. Commun.32411861193PubMedCrossRefGoogle Scholar
  59. 59.
    Ogunbodede, E.Q. 2004Intl. Dent. J.54352360Google Scholar
  60. 60.
    Lee, N.S., Dohjima, T., Bauer, G., Li, H., Li, M.J., Ehsani, A., Salvaterra, P., Rossi, J. 2002Nat. Biotechnol.20500505PubMedGoogle Scholar
  61. 61.
    Jacque, J.M., Triques, K., Stevenson, M. 2002Nature418435438PubMedCrossRefGoogle Scholar
  62. 62.
    Coffin, J.M. 1986Cell4614PubMedCrossRefGoogle Scholar
  63. 63.
    Roberts, J.D., Bebenek, K., Kunkel, T.A. 1988Science24211711173PubMedGoogle Scholar
  64. 64.
    Boden, D., Pusch, O., Lee, F., Tucker, L., Ramratnam, B. 2003J. Virol.7711531155CrossRefGoogle Scholar
  65. 65.
    Das, A.T., Brummelkamp, T.R., Westerhout, E.M., Vink, M., Madiredjo, M., Bernards, R., Berkhout, B. 2004J. Virol.17826012605CrossRefGoogle Scholar
  66. 66.
    Westerhout, E.M., Ooms, M., Vink, M., Das, A.T., Berkhout, B. 2005Nucl. Acids Res.33796804PubMedCrossRefGoogle Scholar
  67. 67.
    L.J. Chang, X. Liu, J. He, Gene Ther. Mar 3 (2005)Google Scholar
  68. 68.
    Leonard, J.N., Schaffer, D.V. 2005J. Virol17916451654CrossRefGoogle Scholar
  69. 69.
    Anderson, J., Banerjea, A., Akkina, R. 2003Oligonucleotides13303312PubMedCrossRefGoogle Scholar
  70. 70.
    Cordelier, P., Morse, B, Strayer, D.S. 2003Oligonucleotides13281294PubMedCrossRefGoogle Scholar
  71. 71.
    Song, E., Lee, S.K., Dykxhoorn, D.M., Novina, C., Zhang, D., Crawford, K., Cerny, J., Sharp, P.A., Lieberman, J., Manjunath, N., Shankar, P. 2003J. Virol.7771747181PubMedCrossRefGoogle Scholar
  72. 72.
    Kameoka, M., Nukuzuma, S., Itaya, A., Tanaka, Y., Ota, K., Ikuta, K., Yoshihara, K. 2004J. Virol.7889318934PubMedCrossRefGoogle Scholar
  73. 73.
    Locarnini, S. 2004Semin Liver Dis.24310PubMedCrossRefGoogle Scholar
  74. 74.
    Zhang, X.N., Xiong, W., Wang, J.D., Hu, KW., Xiang, L., Yuan, Z.H. 2004World J. Gastroenterol.1029672971PubMedGoogle Scholar
  75. 75.
    Chen, Y., Du, D., Wu, J., Chan, C.P., Tan, Y., Kung, H.F., He, M.L. 2003Biochem. Biophys. Res. Commun.311398404PubMedCrossRefGoogle Scholar
  76. 76.
    Giladi, H., Ketzinel-Gilad, M., Rivkin, L., Felig, Y., Nussbaum, O., Galun, E. 2003Mol. Ther.8769776PubMedCrossRefGoogle Scholar
  77. 77.
    Uprichard, S.L., Boyd, B., Althage, A., Chisari, F.V. 2005Proc. Natl. Acad. Sci. USA102773778PubMedCrossRefGoogle Scholar
  78. 78.
    Bhuyar, P.K., Kariko, K., Capodici, J., Lubinski, J., Hook, L.M., Friedman, H.M., Weissman, D. 2004J. Virol.781027610281CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  1. 1.Virology DivisionKimron Veterinary instituteBeit-DaganIsrael

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