Advertisement

Molecular genetic analyses of parapoxviruses pathogenic for humans

  • A. Mercer
  • S. Fleming
  • A. Robinson
  • P. Nettleton
  • H. Reid

Summary

The current members of the genus parapoxvirus are orf virus (ORFV), bovine papular stomatitis virus (BPSV), pseudocowpoxvirus (PCPV) and parapoxvirus of red deer in New Zealand (PVNZ). BPSV and PCPV are maintained in cattle while ORFV is maintained in sheep and goats, but all three are zoonoses. Only the recently reported PVNZ has yet to be recorded as infecting humans. Tentative members of the genus are camel contagious ecthyma virus, chamois contagious ecthyma virus and sealpoxvirus.

The separation of the parapoxviruses into 4 distinct groups has been based on natural host range, pathology and, more recently, on restriction endonuclease and DNA/DNA hybridisation analyses. The latter studies have shown that the parapoxviruses share extensive homology between central regions of their genomes, but much lower levels of relatedness within the genome termini.

The high G+C content of parapoxvirus DNA is in contrast to most other poxviruses and suggests that a significant genetic divergence from other genera of this family has occurred. DNA sequencing of portions of the genome of ORFV, the type species of the genus, has allowed a detailed comparison with the fully sequenced genome of the orthopoxvirus, vaccinia virus (VACV). These studies have provided a genetic map of ORFV and revealed a central core of 88 kbp within which the genomic content was strikingly similar to that of VACV. This conservation is not maintained in the genome termini where insertions, deletions and translocations have occurred.

The characterisation of specific ORFV genes may lead to the construction of attenuated vaccine strains in which genes such as those with the potential to interfere with the immune response of the host have been deleted. The current ORFV vaccines are living unattenuated virus and vaccination lesions produce virus which contaminates the environment in a manner similar to natural infection. The virus in scab material is relatively resistant to inactivation and this virus both perpetuates the disease in sheep and provides the most likely source of human infections. A vaccine which immunises animals without perpetuating the disease could be the best way of reducing the incidence of ORFV infection of humans. It is likely that protection against infection by ORFV is cell mediated and will require the endogenous production of relevant antigens. We have recently constructed a series of VACV recombinants each of which contains a large multigene fragment of ORFV DNA. Together the recombinants represent essentially all of the ORFV genome in an overlapping manner. Vaccination of sheep with the recombinant library provided protection against challenge with virulent ORFV. Further studies with this library may enable dominant protective antigens of ORFV to be identified and lead to their incorporation into a subunit vaccine.

Keywords

Vaccinia Virus Molecular Genetic Analysis Genome Terminus Contagious Ecthyma Total Clinical Score 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Agger WA, Webster SB (1983) Human orf infection complicated by erythema multiformae. Cutis 31: 334–338PubMedGoogle Scholar
  2. 2.
    Bainton RH (1950) Here I stand. The life of Martin Luther. Abingdon-Cokesbury Press, New YorkGoogle Scholar
  3. 3.
    Blakemore F, Abdussalam M, Goldsmith WN (1948) A case of orf (contagious pustular dermatitis): identification of the virus. Br J Dermatol 60: 404–409CrossRefGoogle Scholar
  4. 4.
    Buddle BM, Pulford HD (1984) Effects of passively acquired antibodies and vaccination on the immune response to contagious ecthyma virus. Vet Microbiol 9: 515–522PubMedCrossRefGoogle Scholar
  5. 5.
    Dupre A, Christol B, Bonafe JL, Lassere J (1981) Orf and atopic dermatitis. Br J Dermatol 105: 103–104PubMedCrossRefGoogle Scholar
  6. 6.
    Erickson GA, Carbrey EA, Gustafson GA (1975) Generalised contagious ecthyma in a sheep rancher: diagnostic considerations. J Am Vet Med Assoc 166: 262–263PubMedGoogle Scholar
  7. 7.
    Fastier LB (1957) Human infections with the virus of ovine contagious pustular dermatitis. N Z Med J 56: 121–123PubMedGoogle Scholar
  8. 8.
    Fleming SB, Blok J, Fraser KM, Mercer AA, Robinson AJ (1993) Conservation of gene structure and arrangement between vaccinia virus and orf virus. Virology 195: 175–184PubMedCrossRefGoogle Scholar
  9. 9.
    Fleming SB, Mercer AA, Fraser KM, Lyttle DJ, Robinson AJ (1992) In vivo recognition of orf virus early transcriptional promoters in a vaccinia virus recombinant. Virology 187: 464–471PubMedCrossRefGoogle Scholar
  10. 10.
    Fraser KM, Hill DF, Mercer AA, Robinson AJ (1990) Sequence analysis of the inverted terminal repetition in the genome of the parapoxvirus, orf virus. Virology 176: 379–389PubMedCrossRefGoogle Scholar
  11. 11.
    Gassmann U, Wyler R, Wittek R (1985) Analysis of parapoxvirus genomes. Arch Virol 83: 17–31PubMedCrossRefGoogle Scholar
  12. 12.
    Groves RW (1991) Human orf and milkers’ nodule: a clinicopathological study. J Am Acad Dermatol 25: 706–711PubMedCrossRefGoogle Scholar
  13. 13.
    Haig DM, Hutchison G, Thomson J, Yirrell D, Reid HW (1996) Cytolytic activity and associated serine protease expression by skin and afferent lymph CD8+ T cells during orf virus reinfection. J Gen Virol 77: 953–961PubMedCrossRefGoogle Scholar
  14. 14.
    Hooser SB, Scherba G, Morin DE, Whiteley HE (1989) A typical contagious ecthyma in a sheep after extensive cutaneous thermal injury. J Am Vet Med Assoc 195: 1255–1256PubMedGoogle Scholar
  15. 15.
    Hunskaar S (1986) Giant orf in a patient with lymphocytic leukaemia. Br J Dermatol 114: 631–634PubMedCrossRefGoogle Scholar
  16. 16.
    Jan CL, L’Haridon R, Madelaine MF, Cornu C, Asso J (1978) Transfer of antibodies against CPD virus through colostrum and milk. Ann Rech Vet 9: 343–346Google Scholar
  17. 17.
    Kempe CH (1960) Studies on smallpox and complications of smallpox vaccination. Pediatrics 26: 176–189PubMedGoogle Scholar
  18. 18.
    Lyttle DJ, Fraser KM, Fleming SB, Mercer AA, Robinson AJ (1994) Homologs of vascular endothelial growth factor are encoded by the poxvirus orf virus. J Virol 68: 84–92PubMedGoogle Scholar
  19. 19.
    Mercer AA, Fraser KM, Stockwell PA, Robinson AJ (1989) A homologue of retroviral pseudoproteases in the parapoxvirus, orf virus. Virology 172: 665–668PubMedCrossRefGoogle Scholar
  20. 20.
    Mercer AA, Green G, Sullivan JT, Robinson AJ, Drillien R (1996) Location, DNA sequence and transcriptional analysis of the DNA polymerase gene of orf virus. J Gen Virol 77: 1563–1568PubMedCrossRefGoogle Scholar
  21. 21.
    Mercer AA, Lyttle DJ, Whelan EM, Fleming SB, Sullivan JT (1995) The establishment of a gene map of orf virus reveals a pattern of genomic organisation that is highly conserved among divergent poxviruses. Virology 212: 698–704PubMedCrossRefGoogle Scholar
  22. 22.
    Mercer AA, Yirrell DL, Reid HW, Robinson AJ (1994) Lack of crossprotection between vaccinia virus and orf virus in hysterectomy-procured, barrier-maintained lambs. Vet Microbiol 41: 373–382PubMedCrossRefGoogle Scholar
  23. 23.
    Naase M, Nicholson BH, Fraser KM, Mercer AA, Robinson AJ (1991) An orf virus sequence showing homology to the 14 K ‘fusion’ protein of vaccinia virus. J Gen Virol 72: 1177–1181PubMedCrossRefGoogle Scholar
  24. 24.
    Nettleton PF, Brebner J, Pow I, Gilray JA, Bell GD, Reid HW (1996) Tissue culture-propagated orf virus vaccine protects lambs from orf virus challenge. Vet Rec 138: 184–186PubMedCrossRefGoogle Scholar
  25. 25.
    O’Neill HC, Brenan M (1987) A role for early cytotoxic T cells in resistance to ectromelia virus infection in mice. J Gen Virol 68: 2669–2673PubMedCrossRefGoogle Scholar
  26. 26.
    Poulain J, Gourreau J-M, Dautigny A (1972) Ecthyme contagieux du mouton; anti-crops seriques neutralisants. Ann Rech Vet 3: 561–579Google Scholar
  27. 27.
    Rafii F, Burger D (1985) Comparison of contagious ecthyma virus genomes by restriction endonucleases. Arch Virol 84: 283–289PubMedCrossRefGoogle Scholar
  28. 28.
    Robinson AJ, Balassu TC (1981) Contagious pustular dermatitis (orf). Vet Bull 51: 771–781Google Scholar
  29. 29.
    Robinson AJ, Barns G, Fraser K, Carpenter E, Mercer AA (1987) Conservation and variation in orf virus genomes. Virology 157: 13–23PubMedCrossRefGoogle Scholar
  30. 30.
    Robinson AJ, Lyttle DJ (1992) Parapoxviruses: their biology and potential as recombinant vaccines. In: Binns M, Smith GL (ed) Recombinant poxviruses. CRC Press, Boca Raton, pp 285–327Google Scholar
  31. 31.
    Robinson AJ, Mercer AA (1988) Orf virus and vaccinia virus do not cross protect in sheep. Arch Virol 101: 255–259PubMedCrossRefGoogle Scholar
  32. 32.
    Robinson AJ, Mercer AA (1995) Parapoxvirus of red deer: evidence for its inclusion as a new member in the genus Parapoxvirus. Virology 208: 812–815PubMedCrossRefGoogle Scholar
  33. 33.
    Robinson AJ, Peteresen GV (1983) Orf virus infection of workers in the meat industry. N Z Med J 96: 81–85PubMedGoogle Scholar
  34. 34.
    Savage J, Black MM (1972) “Giant orf” of finger in a patient with a lymphoma. Proc R Soc Med 64: 766–768Google Scholar
  35. 35.
    Sharma DP, Ramsay AJ, Maguire DJ, Rolph MS, Ramshaw IA (1996) Interleukin-4 mediates down regulation of antiviral cytokine expression and cytotoxic T-lymphocyte responses and exacerbates vaccinia virus infection in vivo. J Virol 70: 7103–7107PubMedGoogle Scholar
  36. 36.
    Sullivan JT, Fleming SB, Robinson AJ, Mercer AA (1995) Sequence and transcriptional analysis of a near-terminal region of the orf virus genome. Virus Genes 11: 21–29PubMedCrossRefGoogle Scholar
  37. 37.
    Sullivan JT, Fraser KM, Fleming SB, Robinson AJ, Mercer AA (1995) Sequence and transcriptional analysis of an orf virus gene encoding ankyrinlike repeat sequences. Virus Genes 9: 277–282PubMedCrossRefGoogle Scholar
  38. 38.
    Sullivan JT, Mercer AA, Fleming SB, Robinson AJ (1994) Identification and characterisation of an orf virus homologue of the vaccinia virus gene encoding the major envelope antigen p37k. J Virology 202: 968–973CrossRefGoogle Scholar
  39. 39.
    Tan ST, Blake GB, Chambers S (1991) Recurrent orf in an immunocompromised host. Br J Plastic Surg 44: 465–467CrossRefGoogle Scholar
  40. 40.
    Vos JC, Mercer AA, Fleming SB, Robinson AJ (1992) In vitro recognition of an orf virus early promotor in a vaccinia virus extract. Arch Virol 123: 223–228PubMedCrossRefGoogle Scholar
  41. 41.
    Wilkinson JD (1977) Orf: a family with unusual complications. Br J Dermatol 97: 447–450PubMedCrossRefGoogle Scholar
  42. 42.
    Wittek R, Kuenzle CC, Wyler R (1979) High G+C content in parapoxvirus DNA. J Gen Virol 43: 231–234PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 1997

Authors and Affiliations

  • A. Mercer
    • 1
    • 3
  • S. Fleming
    • 1
  • A. Robinson
    • 1
  • P. Nettleton
    • 2
  • H. Reid
    • 2
  1. 1.Virus Research Unit and Centre for Gene ResearchUniversity of OtagoDunedinNew Zealand
  2. 2.Moredun Research InstituteEdinburghUK
  3. 3.Virus Research Unit, Department of MicrobiologyUniversity of OtagoDunedinNew Zealand

Personalised recommendations