Virus Genes

, Volume 35, Issue 3, pp 753–766 | Cite as

Comparative sequence analysis of a highly oncogenic but horizontal spread-defective clone of Marek’s disease virus

  • Stephen J. Spatz
  • Yuguang Zhao
  • Lawrence Petherbridge
  • Lorraine P. Smith
  • Susan J. Baigent
  • Venugopal Nair
Original Paper

Abstract

Marek’s disease virus (MDV) is a cell-associated alphaherpesvirus that induces rapid-onset T-cell lymphomas in poultry. MDV isolates vary greatly in pathogenicity. While some of the strains such as CVI988 are non-pathogenic and are used as vaccines, others such as RB-1B are highly oncogenic. Molecular determinants associated with differences in pathogenicity are not completely understood. Comparison of the genome sequences of phenotypically different strains could help to identify molecular determinants of pathogenicity. We have previously reported the construction of bacterial artificial chromosome (BAC) clones of RB-1B from which fully infectious viruses could be reconstituted upon DNA transfection into chicken cells. MDV reconstituted from one of these clones (pRB-1B-5) showed similar in vitro and in vivo replication kinetics and oncogenicity as the parental virus. However, unlike the parental RB-1B virus, the BAC-derived virus showed inability to spread between birds. In order to identify the unique determinants for oncogenicity and the ‘‘non-spreading phenotype’’ of MDV derived from this clone, we determined the full-length sequence of pRB-1B-5. Comparative sequence analysis with the published sequences of strains such as Md5, Md11, and CVI988 identified frameshift mutations in RLORF1, protein kinase (UL13), and glycoproteins C (UL44) and D (US6). Comparison of the sequences of these genes with the parental virus indicated that the RLORF1, UL44, and US6 mutations were also present in the parental RB-1B stock of the virus. However with regard to UL13 mutation, the parental RB-1B stock appeared to be a mixture of wild type and mutant viruses, indicating that the BAC cloning has selected a mutant clone. Although further studies are needed to evaluate the role of these genes in the horizontal-spreading defective phenotype, our data clearly indicate that mutations in these genes do not affect the oncogenicity of MDV.

Keywords

Marek’s disease Gallid herpesvirus type 2 Oncogenicity Shedding-defective Genome Sequence 

References

  1. 1.
    A.S. Anderson, M.S. Parcells, R.W. Morgan, J. Virol. 72, 2548–2553 (1998)PubMedGoogle Scholar
  2. 2.
    S.J. Baigent, L.J. Petherbridge, K. Howes, L.P. Smith, R.J. Currie, V.K. Nair, J. Virol. Methods 123, 53–64 (2005)PubMedCrossRefGoogle Scholar
  3. 3.
    A.D. Barrow, S.C. Burgess, S.J. Baigent, K. Howes, V.K. Nair, J. Gen. Virol. 84, 2635–2645 (2003)PubMedCrossRefGoogle Scholar
  4. 4.
    J. Besemer, M. Borodovsky, Nucleic Acids Res. 33, W451–W454 (2005)PubMedCrossRefGoogle Scholar
  5. 5.
    C. Blondeau, N. Chbab, C. Beaumont, K. Courvoisier, N. Osterrieder, J.-F. Vautherot, C. Denesvre, Vet. Res. 38, 419–433 (2007)PubMedCrossRefGoogle Scholar
  6. 6.
    A.C. Brown, S.J. Baigent, L.P. Smith, J.P. Chattoo, L.J. Petherbridge, P. Hawes, M.J. Allday, V. Nair, Proc. Natl. Acad. Sci. USA 103, 1687–1692 (2006)PubMedCrossRefGoogle Scholar
  7. 7.
    P. Brunovskis, L.F. Velicer, Virology 206, 324–338 (1995)PubMedCrossRefGoogle Scholar
  8. 8.
    B.W. Calnek, Crit. Rev. Microbiol. 12, 293–320 (1986)PubMedCrossRefGoogle Scholar
  9. 9.
    B.W. Calnek, in Curr Top Microbiol Immunol, vol. 255, ed. by K. Hirai (Springer-Verlag, Berlin, 2001) pp. 25–55Google Scholar
  10. 10.
    J.H. Chi, C.A. Harley, A. Mukhopadhyay, D.W. Wilson, J. Gen. Virol. 86, 253–261 (2005)PubMedCrossRefGoogle Scholar
  11. 11.
    F. Corpet, Nucleic Acids Res. 16, 10881–10890 (1988)PubMedCrossRefGoogle Scholar
  12. 12.
    P.M. Coussens, L.F. Velicer, J. Virol. 62, 2373–2379 (1988)PubMedGoogle Scholar
  13. 13.
    F. Dorange, B.K. Tischer, J.F. Vautherot, N. Osterrieder, J. Virol. 76, 1959–1970 (2002)PubMedCrossRefGoogle Scholar
  14. 14.
    L. Fragnet, M.A. Blasco, W. Klapper, D. Rasschaert, J. Virol. 77, 5985–5996 (2003)PubMedCrossRefGoogle Scholar
  15. 15.
    W. Fuchs, B.G. Klupp, H. Granzow, C. Hengartner, A. Brack, A. Mundt, L.W. Enquist, T.C. Mettenleiter, J. Virol. 76, 8208–8217 (2002)PubMedCrossRefGoogle Scholar
  16. 16.
    H. Hu, J.I. Cohen, Virology 337, 304–311 (2005)PubMedCrossRefGoogle Scholar
  17. 17.
    Y. Izumiya, H.K. Jang, M. Sugawara, Y. Ikeda, R. Miura, Y. Nishimura, K. Nakamura, T. Miyazawa, C. Kai, T. Mikami, J. Gen. Virol. 80(Pt 9), 2417–2422 (1999)PubMedGoogle Scholar
  18. 18.
    K.W. Jarosinski, N. Osterrieder, V.K. Nair, K.A. Schat, J. Virol. 79, 11647–11659 (2005)PubMedCrossRefGoogle Scholar
  19. 19.
    K.W. Jarosinski, K.A. Schat, Virus Genes 34, 9–22 (2007)PubMedCrossRefGoogle Scholar
  20. 20.
    D.C. Johnson, M.T. Huber, J. Virol. 76, 1–8 (2002)PubMedCrossRefGoogle Scholar
  21. 21.
    K. Katoh, K. Kuma, H. Toh, T. Miyata, Nucleic Acids Res. 33, 511–518 (2005)PubMedCrossRefGoogle Scholar
  22. 22.
    T.K. Kenyon, J.I. Cohen, C. Grose, J. Virol. 76, 10980–10993 (2002)PubMedCrossRefGoogle Scholar
  23. 23.
    B.G. Klupp, H. Granzow, G.M. Keil, T.C. Mettenleiter, J. Virol. 80, 6235–6246 (2006)PubMedCrossRefGoogle Scholar
  24. 24.
    M. Kozak, Nucleic Acids Res. 15, 8125–8148 (1987)PubMedCrossRefGoogle Scholar
  25. 25.
    S. Kumar, K. Tamura, M. Nei, Brief Bioinform. 5, 150–163 (2004)PubMedCrossRefGoogle Scholar
  26. 26.
    L.F. Lee, P. Wu, D. Sui, D. Ren, J. Kamil, H.J. Kung, R.L. Witter, Proc. Natl. Acad. Sci. USA 97, 6091–6096 (2000)PubMedCrossRefGoogle Scholar
  27. 27.
    H.C. Liu, E.J. Soderblom, M.B. Goshe, J. Virol. Methods 135, 66–75 (2006)PubMedCrossRefGoogle Scholar
  28. 28.
    K. Maotani, A. Kanamori, K. Ikuta, S. Ueda, S. Kato, K. Hirai, J. Virol. 58, 657–660 (1986)PubMedGoogle Scholar
  29. 29.
    T.C. Mettenleiter, J. Virol. 76, 1537–1547 (2002)PubMedCrossRefGoogle Scholar
  30. 30.
    T.C. Mettenleiter, Vet. Microbiol. 113, 163–169 (2006)PubMedCrossRefGoogle Scholar
  31. 31.
    J.F. Moffat, L. Zerboni, P.R. Kinchington, C. Grose, H. Kaneshima, A.M. Arvin, J. Virol. 72, 965–974 (1998)PubMedGoogle Scholar
  32. 32.
    J.F. Moffat, L. Zerboni, M.H. Sommer, T.C. Heineman, J.I. Cohen, H. Kaneshima, A.M. Arvin, Proc. Natl. Acad. Sci. USA 95, 11969–11974 (1998)PubMedCrossRefGoogle Scholar
  33. 33.
    R.W. Morgan, A. Anderson, J. Kent, M.S. Parcells, in Current Research on Marek’s Disease, ed. by R.F. Silva, H.H. Cheng, P.M. Coussens (American Association of Avian Pathologists, Kennett Square, Pennsylvania, 1996), pp. 207–212Google Scholar
  34. 34.
    M. Niikura, J. Dodgson, H. Cheng, Arch. Virol. 151, 537–549 (2005)PubMedCrossRefGoogle Scholar
  35. 35.
    M. Niikura, H.C. Liu, J.B. Dodgson, H.H. Cheng, Poult. Sci. 83, 1117–1123 (2004)PubMedGoogle Scholar
  36. 36.
    M. Niikura, R.L. Witter, H.K. Jang, M. Ono, T. Mikami, R.F. Silva, Acta Virol. 43, 159–163 (1999)PubMedGoogle Scholar
  37. 37.
    Y. Nishiyama, Rev. Med. Virol. 14, 33–46 (2004)PubMedCrossRefGoogle Scholar
  38. 38.
    K.J. O’Regan, M.A. Bucks, M.A. Murphy, J.W. Wills, R.J. Courtney, Virology 358, 192–200 (2007)PubMedCrossRefGoogle Scholar
  39. 39.
    K. Ohashi, P.H. O’Connell, K.A. Schat, Virology 199, 275–283 (1994)PubMedCrossRefGoogle Scholar
  40. 40.
    N. Osterrieder, Virus Res. 59, 165–177 (1999)PubMedCrossRefGoogle Scholar
  41. 41.
    N. Osterrieder, J.P. Kamil, D. Schumacher, B.K. Tischer, S. Trapp, Nat. Rev. Microbiol. 4, 283–294 (2006)PubMedCrossRefGoogle Scholar
  42. 42.
    M.S. Parcells, A.S. Anderson, R.W. Morgan, Virus Genes 9, 5–13 (1994)PubMedCrossRefGoogle Scholar
  43. 43.
    L. Petherbridge, A.C. Brown, S.J. Baigent, K. Howes, M.A. Sacco, N. Osterrieder, V.K. Nair, J. Virol. 78, 13376–13380 (2004)PubMedCrossRefGoogle Scholar
  44. 44.
    S.M. Reddy, D. Sui, P. Wu, L. Lee, Acta Virol. 43, 174–180 (1999)PubMedGoogle Scholar
  45. 45.
    F.A. Rey, EMBO Rep. 7, 1000–1005 (2006)PubMedCrossRefGoogle Scholar
  46. 46.
    B.J. Ryckman, R.J. Roller, J. Virol. 78, 399–412 (2004)PubMedCrossRefGoogle Scholar
  47. 47.
    A.A. Schaffer, L. Aravind, T.L. Madden, S. Shavirin, J.L. Spouge, Y.I. Wolf, E.V. Koonin, S.F. Altschul, Nucleic Acids Res. 29, 2994–3005 (2001)PubMedCrossRefGoogle Scholar
  48. 48.
    K.A. Schat, Cancer Surv. 6, 1–37 (1987)PubMedGoogle Scholar
  49. 49.
    K.A. Schat, B.W. Calnek, J. Fabricant, Avian Pathol. 11, 593–605 (1982)PubMedGoogle Scholar
  50. 50.
    D. Schumacher, B.K. Tischer, W. Fuchs, N. Osterrieder, J. Virol. 74, 11088–11098 (2000)PubMedCrossRefGoogle Scholar
  51. 51.
    D. Schumacher, B.K. Tischer, S.M. Reddy, N. Osterrieder, J. Virol. 75, 11307–11318 (2001)PubMedCrossRefGoogle Scholar
  52. 52.
    D. Schumacher, B.K. Tischer, S. Trapp, N. Osterrieder, J. Virol. 79, 3987–3997 (2005)PubMedCrossRefGoogle Scholar
  53. 53.
    B. Silva, L.F. Lee, M. Heidari, I. Gimeno, S. Spatz, J. Zelepsky, in 4th International Workshop on the Molecular Pathogenesis of Marek’s Disease Virus, ed. by M.S. Parcells, R.W. Morgan, J. Burnside, C.J. Schmidt, E.L. Bernberg, C. Kenny, E. Eppler (University of Delaware, Newark, Delaware, 2006), p. 28Google Scholar
  54. 54.
    S.J. Spatz, L. Petherbridge, Y. Zhao, V. Nair, J. Gen. Virol. 88, 1080–1096 (2007)PubMedCrossRefGoogle Scholar
  55. 55.
    S.J. Spatz, R.F. Silva, Virus Genes 35, 41–53 (2006)PubMedCrossRefGoogle Scholar
  56. 56.
    R. Staden, K.F. Beal, J.K. Bonfield, Methods Mol. Biol. 132, 115–130 (2000)PubMedGoogle Scholar
  57. 57.
    B.K. Tischer, D. Schumacher, D. Chabanne-Vautherot, V. Zelnik, J.F. Vautherot, N. Osterrieder, J. Virol. 79, 5889–5899 (2005)PubMedCrossRefGoogle Scholar
  58. 58.
    B.K. Tischer, D. Schumacher, M. Messerle, M. Wagner, N. Osterrieder, J. Gen. Virol. 83, 997–1003 (2002)PubMedGoogle Scholar
  59. 59.
    S. Trapp, M.S. Parcells, J.P. Kamil, D. Schumacher, B.K. Tischer, P.M. Kumar, V.K. Nair, N. Osterrieder, J. Exp. Med. 203, 1307–1317 (2006)PubMedCrossRefGoogle Scholar
  60. 60.
    E.R. Tulman, C.L. Afonso, Z. Lu, L. Zsak, D.L. Rock, G.F. Kutish, J. Virol. 74, 7980–7988 (2000)PubMedCrossRefGoogle Scholar
  61. 61.
    K. Venugopal, Res. Vet. Sci. 69, 17–23 (2000)PubMedCrossRefGoogle Scholar
  62. 62.
    V. Vittone, E. Diefenbach, D. Triffett, M.W. Douglas, A.L. Cunningham, R.J. Diefenbach, J. Virol. 79, 9566–9571 (2005)PubMedCrossRefGoogle Scholar
  63. 63.
    F. Wagenaar, J.M. Pol, B. Peeters, A.L. Gielkens, N. de Wind, T.G. Kimman, J. Gen. Virol. 76(Pt 7), 1851–1859 (1995)PubMedCrossRefGoogle Scholar
  64. 64.
    M. Wagner, Z. Ruzsics, U.H. Koszinowski, Trends Microbiol. 10, 318–324 (2002)PubMedCrossRefGoogle Scholar
  65. 65.
    H. Yamada, Y.M. Jiang, S. Oshima, T. Daikoku, Y. Yamashita, T. Tsurumi, Y. Nishiyama, J. Gen. Virol. 79(Pt 8), 1989–1995 (1998)PubMedGoogle Scholar
  66. 66.
    V. Zelnik, V. Majerciak, D. Szabova, H. Geerligs, J. Kopacek, L.J. Ross, J. Pastorek, Acta Virol. 43, 164–168 (1999)PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Stephen J. Spatz
    • 1
  • Yuguang Zhao
    • 2
  • Lawrence Petherbridge
    • 2
  • Lorraine P. Smith
    • 2
  • Susan J. Baigent
    • 2
  • Venugopal Nair
    • 2
  1. 1.Southeast Poultry Research Laboratory, Agricultural Research Service, United States Department of AgricultureAthensUSA
  2. 2.Institute for Animal Health, Compton LaboratoryComptonUK

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