Abstract
Highly contagious pustular skin infections of sheep, goats and cattle that were unwittingly transmitted to humans from close contact with infected animals, have been the scourge of shepherds, herdsmen and dairy farmers for centuries. In more recent times we recognise that these proliferative pustular lesions are likely to be caused by a group of zoonotic viruses that are classified as parapoxviruses. In addition to infecting the above ungulates, parapoxviruses have more recently been isolated from seals, camels, red deer and reindeer and most have been shown to infect man. The parapoxviruses have one of the smallest genomes of the poxvirus family (140 kb) yet share over 70% of their genes with the most virulent members. Like other poxviruses, the central core of the genomes encode factors for virus transcription and replication, and structural proteins, whereas the terminal regions encode accessory factors that give the parapoxvirus group many of its unique features. Several genes of parapoxviruses are unique to this genus and encode factors that target inflammation, the innate immune responses and the development of acquired immunity. These factors include a homologue of mammalian interleukin (IL)-10, a chemokine binding protein and a granulocyte-macrophage colony stimulating factor /IL-2 binding protein. The ability of this group to reinfect their hosts, even though a cell-mediated memory response is induced during primary infection, may be related to their epitheliotropic niche and the immunomodulators they produce. In this highly localised environment, the secreted immunomodulators only interfere with the local immune response and thus do not compromise the host’s immune system. The discovery of a vascular endothelial growth factor-like gene may explain the highly vascular nature of parapoxvirus lesions. There are many genes of parapoxviruses which do not encode polypeptides with significant matches with protein sequences in public databases, separating this genus from most other mammalian poxviruses. These genes appear to be involved in inhibiting apoptosis, manipulating cell cycle progression and degradation of cellular proteins that may be involved in the stress response, thus allowing the virus to subvert intracellular antiviral mechanisms and enhance the availability of cellular molecules required for replication. Parapoxviruses in common with Molluscum contagiosum virus lack a number of genes that are highly conserved in other poxviruses, including factors for nucleotide metabolism, serine protease inhibitors and kelch-like proteins. It is apparent that parapoxviruses have evolved a unique repertoire of genes that have allowed adaptation to the highly specialised environment of the epidermis.
Chapter PDF
Similar content being viewed by others
Keywords
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.
References
Robinson AJ, Lyttle DJ (1992) Parapoxviruses: their biology and potential as recombinant vaccines. In: M Binns, GL Smith (eds): Recombinant poxviruses. CRC Press, Boca Raton, 285–327
Downie AW, Dumbell KR (1956) Poxviruses. Annu Rev Microbiol 10: 237–252
Andrewes C, Pereira (eds) (1964) Viruses of vertebrates. Baillière, Tindall, Cassell, London
Wildy P (1971) Classification and nomenclature of viruses. First report of the International Committee on Nomenclature of Viruses. Monogr Virol 5: 28; cited in [1]
Fenner F (1976) Classification and nomenclature of viruses. Second report of the International Committee on Taxonomy of Viruses. Intervirology 7: 1–115
Fauquet CM, Mayo, MA, Maniloff J, Desselberger U, Ball LA (eds) (2005) Virus Taxonomy. Eighth report of the International committee on Taxonomy of viruses. Academic Press, Elservier, London, 117–133
Thomas K, Tompkins DM, Sainsbury AW, Wood A, Dalziel R, Nettleton PF, McInnes CJ (2003) A novel poxvirus lethal to red squirrels (Sciurus vulgaris). J Gen Virol 84: 3337–3341
Steeb (1787) Von der Schaf-Raude (Grind); cited in: H. Nürnberg: über den ansteckenden Maulgrind der Schafe und Ziegen. Dr. med. vet. Thesis, Friedrich-Wilhelms-Universität, Berlin
Walley T (1890) Contagious dermatitis: “orf” in sheep. J Comp Pathol Ther 3: 357–360
Hansen (1879) Tidsskr Vet 9: 298; cited in: Hodgson-Jones IS (1951) Orf in London. Br Med J 1: 795
Aynaud M (1923) La stomatite pustuleuse contagieuse des ovins (chancre du mouton. Ann Inst Pasteur (Paris) 36: 498–527
Bonnevie P (1937) Milker’s warts: infection from “false cowpox” with a paravaccinia virus. Br J Dermatol 49: 165; cited in: M Binns, GL Smith (eds): Recombinant poxviruses. CRC Press, Boca Raton
Lipschutz B (1932) Paravaccine, Julius Springer, Berlin; cited in: M Binns, GL Smith (eds): Recombinant poxviruses. CRC Press, Boca Raton
Griesemer RA, Cole CR (1960) Bovine papular stomatitis. I. Recognition in the United States. J Am Vet Med Assoc 137: 404–410
Degive A (1884) Une affection-type ou maladie inedite-la stomatite papillaire ou papillomateuse-observee sur quatre genesis. Ann Med Vet 33: 369; cited in: M Binns, GL Smith (eds): Recombinant poxviruses. CRC Press, Boca Raton
Plowright WR, Ferris RD (1959) Papular stomatitis of cattle. II. Reproduction of the disease with culture-passaged virus. Vet Rec 71: 828; cited in: M Binns, GL Smith (eds): Recombinant poxviruses. CRC Press, Boca Raton
Griesemer RA, Cole CR (1961) Bovine papular stomatitis. II. The experimentally produced disease. Am J Vet Res 22: 473–481
Carson CA, Kerr KM (1967) Bovine papular stomatitis with apparent transmission to man. J Am Vet Med Assoc 151:183–187
Rosliakov AA (1972) Comparative ultrastructure of viruses of camel pox, poxlike disease of camels (AUZDUK) and contagious ecthyma of sheep. Voprosi Virusol 17: 26–30
Dashtseren T, Solovyev BV, Varejka F, Khokhoo A (1984) Camel contagious ecthyma (Pustular Dermatitis). Acta Virol 28:128–133
Jezek Z, Kriz B, Rothbauer V (1983) Camelpox and its risk to the human population. J Hyg Epidemiol Microbiol Immunol 27: 29–42
Munz E, Schillinger D, Reimann M, Mahnel H (1986) Electron microscopical diagnosis of Ecthyma contagiosum in camels (Camelus dromedaries). First report of the disease in Kenya. Zentralbl Veterinarmed B 33: 73–77
Azwai SM, Carter SD, Woldehiwet Z (1995) Immune responses of the camel (Camelus dromedaries) to contagious ecthyma (Orf) virus infection. Vet Microbiol 47: 119–131
Hartung J (1980) Contagious ecthyma of sheep (cases in man, dog, alpaca and camel). Tieraerztl Prax 8: 435–438
Wilson TM, Poglayen-Neuwall I (1971) Pox in South American sea lions (Otaria byronia). Can J Comp Med 35: 174–177
Wilson T, Cheville N, Karstad L (1969) Seal pox. Bull Wild Dis Assoc 5: 412–418
Wilson TM, Dykes RW, Tsai KS (1972) Pox in young, captive harbor seals.J Am Vet Med Assoc 161: 611–617
Becher P, Konig M, Muller G, Siebert U, Thiel HJ (2002) Characterization of sealpox virus, a separate member of the parapoxviruses. Arch Virol 147: 1133–1140
Hadlow WJ, Cheville NF, Jellison WL (1980) Occurence of pox in northern fur seal on the Pribilof Islands in 1951. J Wildl Dis 16: 305–312
Simpson VR, Stuart NC, Stack MJ, Ross HA, Head JC (1994) Parapox infection in grey seals (Halichoerus grypus) in Cornwall. Vet Rec 134: 292–296
Osterhaus AD, Broeders HW, Visser IK, Teppema JS, Vedder EJ (1990) Isolation of an orthopoxvirus from pox-like lesions of a grey seal (Halichoerus grypus). Vet Rec 127: 91–92
Hicks BD, Worthy GA (1987) Sealpox in captive grey seals (Halichoerus grypus) and their handlers. J Wildl Dis 23: 1–6
Tryland M, Klein J, Nordoy ES, Blix AS (2005) Isolation and partial characterization of a parapoxvirus isolated from a skin lesion of a Weddell seal. Virus Res 108: 83–87
Horner GW, Robinson AJ, Hunter R, Cox BT, Smith R (1987) Parapoxvirus infections in New Zealand farmed red deer. NZ Vet J 35: 41–45
Robinson AJ, Mercer AA (1995) Parapoxvirus of red deer: evidence for its inclusion as a new member in the genus parapoxvirus. Virology 208: 812–815
Buttner M, von Einem C, McInnes C, Oksanen A (1995) Clinical findings and diagnosis of a severe parapoxvirus epidemic in Finnish reindeer. Tierarztl Prax 23: 614–618
Tryland M, Josefsen TD, Oksanen A, Aschfalk A (2001) Parapoxvirus infection in Norwegian semi-domesticated reindeer (Rangifer tarandus tarandus). Vet Rec 149, 394–395
Tikkanen MK, McInnes CJ, Mercer AA, Buttner M, Tuimala J, Hirvela-Koski V, Neuvonen E, Huovilainen (2004) Recent isolates of parapoxvirus of Finnish reindeer (Rangifer tarandus tarandus) are closely related to bovine pseudocowpox virus. J Gen Virol 85: 1413–1418
Buttner M, Rziha HJ (2002) Parapoxviruses: from the lesion to the viral genome. J Vet Med B Infect Dis Vet Public Health 49: 7–16
Reid HW (1991) Orf. In: WB Martin, ID Aitken (eds) Diseases of sheep. Blackwell, London, 265–269
Lloyd JB (1996) A study of the immune response of sheep to orf virus. Ph.D thesis, Department of Veterinary Pathology, University of Sydney, Sydney
Blood DC, Radostits OM, Henderson JA, Arundel JH, Gay CC (1983) Veterinary medicine: a textbook of the diseases of cattle, sheep, goats and horses. Bailliere Tindall, London, 945–946
Greig A, Linklater KA, Clark WA (1984) Persistent orf in a ram. Vet Rec 115: 149
McKeever DJ (1984) Persistent orf. Vet Rec 115: 334–335
Inoshima Y, Yamamoto Y, Takahashi T, Shino M, Katsumi A, Shimizu S, Sentsui H (2001) Serological survey of parapoxvirus infection in wild ruminants in Japan in 1996-99. Epidemiol Infect 126: 153–156
Inoshima Y, Murakami K, Wu D, Sentsui H (2002) Characterization of parapoxviruses circulating among wild Japanese serows (Capricornis crispus). Microbiol Immunol 46: 583–587
Maollin AS, Zessin KH (1988) Outbreak of camel contagious ecthyma in central Somalia. Trop Anim Health Prod 20: 185
Gitao CG (1994) Outbreaks of contagious ecthyma in camels (Camelus dromedaries) in the Turkana district of Kenya. Rev Sci Tech 13: 939–945
Klein J, Tryland M (2005) Characterisation of parapoxviruses isolated from Norwegian semi-domesticated reindeer (Rangifer tarandus tarandus). Virol J 2: 79
Afonso CL, Delhon G, Tulman ER, Lu Z, Zsak A, Becerra VM, Zsak L, Kutish GF, Rock DL (2005) Genome of deerpox virus. J Virol 79: 966–977
Abu Elzein EM, Housawi FM (1997) Severe long-lasting contagious ecthyma infection in a goat’s kid. Zentralbl Veterinarmed B 44: 561–564
Haig DM, Mercer AA (1998) Ovine diseases. Orf. Vet Res 29:311–326
Nettleton PF, Munro R, Pow I, Gilray J, Gray EW, Reid HW (1995) Isolation of a parapoxvirus from a grey seal (Halichoerus grypus). Vet Rec 137: 562–564
McKeever DJ, Jenkinson DM, Hutchison G, Reid HW (1988) Studies of the pathogenesis of orf virus infection in sheep. J Comp Pathol 99: 317–328
Jenkinson DM, McEwan PE, Onwuka SK, Moss VA, Elder HY, Hutchison G, Reid HW (1990) The polymorphonuclear and mast cell responses in ovine skin infected with orf virus. Vet Dermatol 1: 71–77
Jenkinson DM, Hutchison G, Onwuka SK, Reid HW (1991) Changes in the MHC class II dendritic cell population of ovine skin in response to orf virus Infection. Vet Dermatol 2: 1–9
Groves RW, Wilson-Jones E, MacDonald DM (1991) Human orf and milkers’ nodule: a clinicopathologic study. J Am Acad Dermatol 25: 706–711
Ghislain PD, Dinet Y, Delescluse J (2001) Orf in urban surroundings and religious practices: a study over a 3-year period. Ann Dermatol Venereol 128: 889–892
Leavell UW, McNamara J, Muelling RJ, Landrum F (1965) Ecthyma contagiosum virus (orf). South Med J 58: 239–243
Becker FT (1940) Milkers nodules. JAMA 115: 2140–2144
Falk ES (1978) Parapoxvirus infections of reindeer and musk ox associated with unusual human infections. Br J Dermatol 99: 647–654
Savage J, Black MM (1972) “Giant orf” of a finger in a patient with lymphoma. Proc R Soc Med 64: 766–768
Tan ST, Blake GB, Chambers S (1991) Recurrent orf in an immunocompromised host. Br J Plastic Surg 44: 465–467
Agger WA, Webster SB (1983) Human orf infection complicated by erythema multiformae. Cutis 31: 334–338
Blakemore F, Abdussalam M, Goldsmith WN (1948) A case of orf (contagious pustular dermatitis): identification of the virus. Br J Dermatol 60: 404–409
Fastier LB (1957) Human infections with the virus of ovine contagious pustular dermatitis. NZ Med J 56: 121–123
Mourtada I, Le Tourneur M, Chevrant-Breton J, Le Gall F (2000) Human orf and erythema multiforme. Ann Dermatol Venereol 127: 397–399
Erickson GA, Carbrey EA, Gustafson GA (1975) Generalised contagious ecthyma in a sheep rancher: diagnostic considerations. J Am Vet Med Assoc 166: 262–263
Sanchez RL, Hebert A, Lucia H, Swedo J (1985) Orf. A case report with histologic, electron microscopic, and immunoperoxidase studies. Arch Pathol Lab Med 109: 166–170
Geerinck K, Lukito G, Snoeck R, De Vos R, De Clercq E, Vanrenterghem Y, Degreef H, Maes B. (2001) A case of human orf in an immunocompromised patient treated successfully with cidofovir cream. J Med Virol 64: 543–549
Abdussalam M, Cosslett VE (1957) Contagious pustular dermatitis. J Comp Pathol 67:145–156
Reczko E (1957) Electronenmikroskopische untersuchungen am virus der stomatitis papulosa. Zentralbl Bakteriol Abt Orig B 169: 425–453
Nagington J, Horne RW (1962) Morphological studies of orf and vaccinia viruses. Virology 16: 248–260
Nagington J, Newton AA, Horne RW (1964) The structure of orf virus. Virology 23: 461–472
Peters D, Muller G, Buttner D (1964) The fine structure of paravaccinia viruses. Virology 23: 609–611
Mitchiner MB (1969) The envelope of vaccinia and orf viruses: an electroncytochemical investigation. J Gen Virol 5: 211–220
Hiramatsu Y, Uno F, Yoshida M, Hatano Y, Nii S (1999) Poxvirus virions: their surface ultrastructure and interaction with the surface membrane of host cells. J Electron Microsc (Tokyo) 48: 937–946
Ballasu TC, Robinson AJ (1987) Orf virus replication in bovine testis cells: kinetics of viral DNA, polypeptide, and infectious virus production and analysis of virion polypeptides. Arch Virol 97: 267–281
Buddle BM, Dellers RW, Schurig GG (1984) Heterogeneity of contagious ecthyma virus isolates. Am J Vet Res 45: 75–79
McKeever DJ, Reid HW, Inglis NF, Herring AJ (1987) A qualitative and quantitative assessment of the humoral antibody response of the sheep to orf virus infection. Vet Microbiol 15: 229–241
Rosenbusch RF, Reed DE (1983) Reaction of convalescent bovine antisera with strain-specific antigens of parapoxviruses. Am J Vet Res 44: 875–878
Thomas V, Flores L, Holowczak JA (1980) Biochemical and electron microscopic studies of the replication and composition of milker’s node virus. J Virol 34: 244–255
Housawi FM, Roberts GM, Gilray JA, Pow I, Reid HW, Nettleton PF, Sumption KJ, Hibma MH, Mercer AA (1998) The reactivity of monoclonal antibodies against orf virus with other parapoxviruses and the identification of a 39 kDa immunodominant protein. Arch Virol 143: 2289–2303
Czerny CP, Waldmann R, Scheubeck T (1997) Identification of three distinct antigenic sites in parapoxviruses. Arch Virol 142: 807–821
Scagliarini A, Ciulli S, Battilani M, Jacoboni I, Montesi F, Casadio R, Prosperi S (2002) Characterisation of immunodominant protein encoded by the F1L gene of orf virus strains isolated in Italy. Arch Virol 147: 1989–1995
Zinoviev VV, Tchikaev NA, Chertov O, Malygin EG (1994) Identification of the gene encoding vaccinia virus immunodominant protein p35. Gene 147: 209–214
da Fonseca FG, Wolffe EJ, Weisberg A, Moss B (2000) Characterization of the vaccinia virus H3L envelope protein: topology and posttranslational membrane insertion via the C-terminal hydrophobic tail. J Virol 74: 7508–7517
da Fonseca FG, Wolffe EJ, Weisberg A, Moss B (2000) Effects of deletion or stringent repression of the H3L envelope gene on vaccinia virus replication. J Virol 74: 7518–7528
Lin CL, Chung CS, Heine HG, Chang W (2000) Vaccinia virus envelope H3L protein binds to cell surface heparan sulfate and is important for intracellular mature virion morphogenesis and virus infection in vitro and in vivo. J Virol 74: 3353–3365
Yirrell DL, Vestey JP, Norval M (1994) Immune responses of patients to orf virus infection. Br J Dermatol 130: 438–443
Smith GL, Vanderplasschen A (1998) Extracellular enveloped vaccinia virus. In: L Enjuanes, SG Siddell, W Spaan (eds): Coronaviruses and Arteriviruses. Plenum Press, London, 395–414
Haig DM, McInnes CJ (2002) Immunity and counter-immunity during infection with the parapoxvirus orf virus. Virus Res 88: 3–16
Buddle BM, Pulford HD (1984) Effect of passively-acquired antibodies and vaccination of the immune response to contagious ecthyma virus. Vet Microbiol 9: 515–522
Robinson AJ, Mercer AA (1988) Orf virus and vaccinia virus do not cross-protect sheep. Arch Virol 101: 255–259
Mercer AA, Yirrell DL, Reid HW, Robinson AJ (1994) Lack of cross-protection between vaccinia virus and orf virus in hysterectomy-procured, barrier maintained lambs. Vet Microbiol 41: 373–382
Jenkinson D, McEwan PE, Onwuka SK, Moss VA, Elder HY, Hutchison G, Reid HW (1990) The pathological changes and polymorphonuclear and mast cell responses in the skin of specific pathogen-free lambs following primary and secondary challenge with orf virus. Vet Dermatol 1: 139–150
Jenkinson DM, Hutchison G, Reid HW (1992) The B and T cell responses to orf virus infection of ovine skin. Vet Dermatol 3: 57–64
Lear A, Hutchison G, Reid HW, Norval M, Haig DM (1996) Phenotypic characterisation of the dendritic cells accumulating in ovine dermis following primary and secondary orf virus infections. Eur J Dermatol 6: 135–140
Anderson IE, Reid HW, Nettleton PF, McInnes CJ, Haig DM (2001) Detection of cellular cytokine mRNA expression during orf virus infection in sheep: differential interferon-gamma mRNA expression by cells in primary versus reinfection skin lesions. Vet Immunol Immunopathol 83: 161–176
Haig DM, Hutchinson 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: 953–961
Yirrell DL, Reid HW, Norval M, Entrican G, Miller HR (1991) Response of efferent lymph and popliteal lymph node to epidermal infection of sheep with orf virus. Vet Immunol Immunopathol 28: 219–235
Yirrell DL, Reid HW, Norval M, Miller HR (1991) Qualitative and quantitative changes in ovine afferent lymph draining the site of epidermal orf virus infection Vet Dermatol 2: 133–141
Haig DM, Entrican G, Yirrell DL, Deane D, Millar HR, Norval M, Reid HW (1992) Differential appearance of interferon and colony stimulating activity in afferent versus efferent lymph following orf virus infection in sheep. Vet Dermatol 3: 221–229
Haig D, Deane D, Percival A, Myatt N, Thomson J, Inglis L, Rothel J, Heng-Fong S, Wood P, Miller HR, Reid HW (1996) The cytokine response of afferent lymph following orf virus reinfection of sheep. Vet Dermatol 7: 11–20
Haig DM, Hopkins J, Miller HR (1999) Local immune responses in afferent and efferent lymph. Immunology 96: 155–163
Haig DM, McInnes CJ, Hutchison G, Seow HF, Reid HW (1996) Cyclosporin A abrogates the acquired immunity to cutaneous reinfection with the parapoxvirus orf virus. Immunology 89: 524–531
Lloyd JB, Gill HS, Haig DM, Husband AJ (2000) In vivo T-cell subset depletion suggests that CD4+ T-cells and a humoral immune response are important for the elimination of orf virus from the skin of sheep. Vet Immunol Immunopathol 74: 249–262
Haig DM, Deane DL, Myatt N, Thomson J, Entrican G, Rothel J, Reid HW (1996) The activation status of ovine CD45R+ and CD45R-efferent lymph T cells after orf virus reinfection. J Comp Pathol 115: 163–174
Deane D, McInnes CJ, Perciva A, Wood A, Thomson J, Lear A, Gilray J, Fleming S, Mercer A, Haig D (2000) Orf virus encodes a novel secreted protein inhibitor of granulocyte-macrophage colony-stimulating factor and interleukin-2. J Virol 74: 1313–1320
Fleming SB, McCaughan CA, Andrews AE, Nash AD, Mercer AA (1997) A homologue of interleukin-10_is encoded by the poxvirus orf virus. J Virol 71: 4857–4861
Seet BT, McCaughan CA, Handel TM, Mercer AA, Brunetti C, McFadden G, Fleming SB (2003) Analysis of an orf virus chemokine-binding protein: Shifting ligand specificities among a family of poxvirus viroceptors. Proc Natl Acad Sci USA 100: 15137–15142
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: 84–92
McInnes CJ, Wood AR, Mercer AA (1998) Orf virus encodes a homolog of the vaccinia virus interferon-resistance gene E3L. Virus Genes 17: 107–115
Haig DM, McInnes CJ, Thomson J, Wood A, Bunyan K, Mercer A (1998) The orf virus OV20.0L gene product is involved in interferon resistance and inhibits an interferon-inducible, double-stranded RNA-dependent kinase. Immunology 93: 335–340
Delhon G, Tulman ER, Afonso CL, Lu Z, de la Concha-Bermejillo A, Lehmkuhl HD, Piccone ME, Kutish GF, Rock DL (2004) Genomes of the parapoxviruses ORF virus and bovine papular stomatitis virus. J Virol 78:168–177
Menna A, Wittek R, Bachmann PA, Mayer A, Wyler R (1979) Physical characterisation of a stomatitis papulosa virus genome: a cleavage map for the restriction endonucleases HindIII and EcoRI. Arch Virol 59: 145–156
Wittek R, Kuenzle CC, Wyler R (1979) High G+C content in parapoxvirus DNA. J Gen Virol 43: 231–234
Wittek R, Herlyn M, Schumperli D, Bachmann PA, Mayr A, Wyler R (1980) Genetic and antigenic heterogeneity of different parapoxvirus strains. Intervirology 13: 33–41
Gassmann U, Wyler R, Wittek R (1985) Analysis of parapoxvirus genomes. Arch Virol 83: 17–31
Wood AR, McInnes CJ (2003) Transcript mapping of the ‘early’ genes of Orf virus. J Gen Virol 84: 2993–2998
McInnes CJ, Wood AR, Nettleton PE, Gilray JA (2001) Genomic comparison of an avirulent strain of Orf virus with that of a virulent wild type isolate reveals that the Orf virus G2L gene is non-essential for replication. Virus Genes 22: 141–150
Haig DM, Thomson J, McInnes CJ, Deane DL, Anderson IE, McCaughan CA, Imlach W, Mercer AA, Howard CJ, Fleming SB (2002) A comparison of the anti-inflammatory and immunostimulatory activities of orf virus and ovine interleukin-10. Virus Res 90: 303–316
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: 175–184
Mercer AA, Lyttle DJ, Whelan EM, Fleming SB, Sullivan JT (1995) The establishment of a genetic map of orf virus reveals a pattern of genomic organization that is highly conserved among divergent poxviruses. Virology 212: 698–704
Robinson AJ, Ellis G, Ballasu T (1982) The genome of orf virus: restriction endonuclease analysis of viral DNA isolated from lesions of orf virus in sheep. Arch Virol 71: 43–55
Robinson AJ, Barns G, Fraser K, Carpenter E, Mercer AA (1987) Conservation and variation in orf virus genomes. Virology 157: 13–23
Mercer AA, Fraser K, Barns G, Robinson AJ (1987) The structure and cloning of orf virus DNA. Virology 157: 1–12
Mercer AA, Fraser KM, Stockwell PA, Robinson AJ (1989) A homologue of retroviral pseudoproteases in the parapoxvirus orf virus. Virology 172: 665–668
Klemperer N, Lyttle D J, Tauzin D, Traktman P, Robinson AJ (1995) Identification and characterization of the orf virus type I topoisomerase. Virology 206, 203–215
Naase M, Nicholson BH, Fraser KM, Mercer AA, Robinson AJ (1991) An orf virus sequence showing homology to the 14K ‘fusion’ protein of vaccinia virus. J Gen Virol 72: 1177–1181
Seet BT, McFadden G (2002) Viral chemokine-binding proteins. J Leukoc Biol 72: 24–34
Sullivan JT, Fraser KM, Fleming SB, Robinson AJ, Mercer AA (1995) Sequence and transcriptional analysis of an orf virus gene encoding ankyrin-like repeat sequences. Virus Genes 93: 277–282
Fleming SB, Fraser KM, Mercer AA, Robinson AJ (1991) Vaccinia virus-like early transcriptional control sequences flank an early gene in orf virus. Gene 97: 207–212
Fleming SB, Mercer AA, Fraser KM, Lyttle DJ, Robinson AJ (1992) In vivo recognition of orf virus early transcriptional promoters in a vaccina virus recombinant. Virology 187: 464–471
Vos JC, Mercer AA, Fleming SB, Robinson AJ (1992) In vitro recognition of an orf virus early promoter in a vaccinia virus extract. Arch Virol 123: 223–228
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: 21–29
Sullivan JT, Mercer AA, Fleming SB, Robinson AJ (1994) Identification and characterization of an orf virus homologue of the vaccinia virus gene encoding the major envelope antigen p37K. Virology 202: 968–973
Mercer AA, Ueda N, Friederichs SM, Hofmann K, Fraser KM, Bateman T, Fleming SB (2006) Comparative analysis of genome sequences of three isolates of Orf virus reveals unexpected sequence variation. Virus Res 116: 146–158
Mercer AA, Fleming SB, Ueda N (2005) F-Box-Like domains are present in most poxvirus ankyrin repeat proteins. Virus Genes 31: 127–133
Inoshima Y, Murakami K, Yokoyama T, Sentsui H (2001) Genetic heterogeneity among parapoxviruses isolated from sheep, cattle and Japanese serows (Capricornis crispus). J Gen Virol 82: 1215–1220
Upton C, Slack S, Hunter AL, Ehlers A, Roper RL (2003) Poxvirus orthologous clusters: toward defining the minimum essential poxvirus genome. J Virol 77: 590–600
Gubser C, Hue S, Kella P, Smith GL (2004) Poxvirus genomes: a phylogenetic analysis. J Gen Virol 85: 105–117
Fleming SB, Lyttle DJ, Sullivan JT, Mercer AA, Robinson AJ (1995) Genomic analysis of a transposition-deletion variant of orf virus reveals a 3.3 kbp region of non-essential DNA. J Gen Virol 76: 2969–2978
Esposito JJ, Cabradilla CD, Nakano JH, Obijeski JF (1981) Intragenomic sequence transposition in monkeypox virus. Virology 109: 231–243
Pickup DJ, Ink BS, Parsons BL, Hu W, Joklik WK (1984) Spontaneous deletions and duplications of sequences in the genome of cowpox virus. Proc Natl Acad Sci USA 81: 6817–6821
Moyer RW, Rothe CT (1980) The white pock mutants of rabbit poxvirus. I. Spontaneous host range mutants contain deletions. Virology 102: 119–132
Kotwal GJ, Moss B (1988) Analysis of a large cluster of nonessential genes deleted from a vaccinia virus terminal transposition mutant. Virology 167: 524–537
Cottone R, Buttner M, Bauer B, Henkel M, Hettich E, Rziha HJ (1998) Analysis of genomic rearrangement and subsequent gene deletion of the attenuated Orf virus strain D 1701. Virus Res 56: 53–67
Lee HJ, Essani K, Smith GL (2001) The genome sequence of Yaba-like disease virus, a yatapoxvirus. Virology 281: 170–192
Tulman ER, Afonso CL, Lu Z, Zsak L, Kutish GF, Rock DL (2001) Genome of lumpy skin disease virus. J Virol 75: 7122–7130
Moore KW, De Waal Malefyte R, Coffman R, O’Garra A (2001) Interleukin-10 and interleukin-10 receptor. Annu Rev Immunol 19: 683–704
Kotenko SV, Saccani S, Izotova LS, Mirochnitchenko OV, Pestka S (2000) Human cytomegalovirus harbors its own unique IL-10 homolog (cmvIL-10). Proc Natl Acad Sci USA 97: 1695–1700
Lockridge KM, Zhou SS, Kravitz RH, Johnson JL, Sawai ET, Blewett EL, Barry PA (2000) Primate cytomegaloviruses encode and express an IL-10-like protein. Virology 268: 272–280
Bartlett NW, Dumoutier L, Renauld JC, Kotenko SV, McVey CE, Lee HJ, Smith GL (2004) A new member of the interleukin 10-related cytokine family encoded by a poxvirus. J Gen Virol 85: 1401–1412
Imlach W, McCaughan CA, Mercer AA, Haig D, Fleming SB (2002) Orf virusencoded interleukin-10 stimulates the proliferation of murine mast cells and inhibits cytokine synthesis in murine peritoneal macrophages. J Gen Virol 83: 1049–1058
Lateef Z, Fleming SB, Halliday G, Faulkner L, Mercer A, Baird M (2003) Orf virus-encoded interleukin-10_inhibits maturation, antigen presentation and migration of murine dendritic cells. J Gen Virol 84: 1101–1109
Zdanov A, Schalk-Hihi C, Gustchina A, Tsang M, Weatherbee J, Wlodawer A (1995) Crystal structure of interleukin-10_reveals the functional dimer with an unexpected topological similarity to interferon gamma. Structure 3: 591–601
Zdanov A, Schalk-Hihi C, Wlodawer A (1996) Crystal structure of human interleukin-10 at 1.6 Å resolution and a model of a complex with its soluble receptor. Protein Sci 5: 1955–1962
Walter MR, Nagabhushan TL (1995) Crystal structure of interleukin 10 reveals an interferon gamma-like fold. Biochemistry 34: 12118–12125
Josephson K, Logsdon NJ, Walter MR (2001) Crystal structure of the IL-10/IL 10R1 complex reveals a shared receptor binding site. Immunity 15: 35–46
MacNeil IA, Suda T, Moore KW, Mosmann TR, Zlotnik A (1990) IL-10, a novel growth cofactor for mature and immature T cells. J Immunol 145: 4167–4173
Go NF, Castle BE, Barrett R, Kastelein R, Dang W, Mosmann TR, Moore KW, Howard M (1990) Interleukin 10, a novel B cell stimulatory factor: unresponsiveness of X chromosome-linked immunodeficiency B cells. J Exp Med 172: 1625–1631
Vieira P, de Waal-Malefyt R, Dang MN, Johnson KE, Kastelein R, Fiorentino DF, deVries JE, Roncarolo MG, Mosmann TR, Moore KW (1991) Isolation and expression of human cytokine synthesis inhibitory factor cDNA clones: homology to Epstein-Barr virus open reading frame BCRFI. Proc Natl Acad Sci USA 88: 1172–1176
Suzuki T, Tahara H, Narula S, Moore KW, Robbins PD, Lotze MT (1995) Viral interleukin 10 (IL-10), the human herpes virus 4 cellular IL-10 homologue, induces local anergy to allogeneic and syngeneic tumors. J Exp Med 182: 477–486
Fickenscher H, Hor S, Kupers H, Knappe A, Wittmann S, Sticht H (2002) The interleukin-10 family of cytokines. Trends Immunol 23: 89–96
Smith C, Smith T, Smolak P, Friend D, Hagen H, Gerhart M, Park L, Pickup D, Torrance D, Mohler K et al (1997) Poxvirus genomes encode a secreted, soluble protein that preferentially inhibits beta chemokine activity yet lacks sequence homology to known chemokine receptors. Virology 236: 316–327
Graham KA, Lalani AS, Macen JL, Ness TL, Barry M, Liu LY, Lucas A, Clark-Lewis I, Moyer RW, McFadden G (1997) The T1/35kDa family of poxvirussecreted proteins bind chemokines and modulate leukocyte influx into virusinfected tissues. Virology 229: 12–24
Rossi D, Zlotnik A (2000) The biology of chemokines and their receptors. Annu Rev Immunol 18: 217–242
Murphy PM, Baggiolini M, Charo IF, Hebert CA, Horuk R, Matsushima K, Miller LH, Oppenheim JJ, Power CA (2000) International union of pharmacology. XXII. Nomenclature for chemokine receptors. Pharmacol Rev 52: 145–176
McInnes CJ, Deane D, Haig D, Percival A, Thomson J, Wood AR (2005) Glycosylation, disulfide bond formation, and the presence of a WSXWS-like motif in the orf virus GIF protein are critical for maintaining the integrity of Binding to ovine granulocyte-macrophage colony-stimulating factor and interleukin-2. J Virol 79: 11205–11213
Ng A, Tscharke DC, Reading PC, Smith GL (2001) The vaccinia virus A41L protein is a soluble 30 kDa glycoprotein that affects virus virulence. J Gen Virol 82: 2095–2105
Ogawa S, Oku A, Sawano A, Yamaguchi S, Yazaki Y, Shibuya M (1998) A novel type of vascular endothelial growth factor, VEGF-E (NZ-7 VEGF), preferentially utilizes KDR/Flk-1 receptor and carries a potent mitotic activity without heparin-binding domain. J Biol Chem 273: 31273–31282
Meyer M, Clauss M, Lepple-Wienhues A, Waltenberger J, Augustin HG, Ziche M, Lanz C, Buttner M, Rziha HJ, Dehio C (1999) A novel vascular endothelial growth factor encoded by Orf virus, VEGF-E, mediates angiogenesis via signalling through VEGFR-2 (KDR) but not VEGFR-1 (Flt-1) receptor tyrosine kinase. EMBO J 18: 363–374
Wise LM, Veikkola T, Mercer AA, Savory LJ, Fleming SB, Caesar C, Vitali A, Makinen T, Alitalo K, Stacker SA (1999) Vascular endothelial growth factor (VEGF)-like protein from orf virus NZ2 binds to VEGFR2 and neuropilin-1. Proc Natl Acad Sci USA 96: 3071–3076
Ueda N, Wise LM, Stacker SA, Fleming SB, Mercer AA (2003) Pseudocowpox virus encodes a homolog of vascular endothelial growth factor. Virology 305: 298–309
He JG, Deng M, Weng SP, Li Z, Zhou SY, Long QX, Wang XZ, Chan SM (2001) Complete genome analysis of the mandarin fish infectious spleen and kidney necrosis iridovirus. Virology 291: 126–139
Lu L, Zhou SY, Chen C, Weng SP, Chan S M, He JG (2005) Complete genome sequence analysis of an iridovirus isolated from the orange-spotted grouper, Epinephelus coioides. Virology 339: 81–100
Ferrara N, Gerber HP, LeCouter J (2003) The biology of VEGF and its receptors. Nat Med 9: 669–676
Stacker SA, Achen MG (1999) The vascular endothelial growth factor family: signalling for vascular development. Growth Factors 17: 1–11
Mercer AA, Wise LM, Scagliarini A, McInnes CJ, Buttner M, Rziha HJ, McCaughan CA, Fleming SB, Ueda N, Nettleton PF (2002) Vascular endothelial growth factors encoded by Orf virus show surprising sequence variation but have a conserved, functionally relevant structure. J Gen Virol 83: 2845–2855
Wise LM, Ueda N, Dryden NH, Fleming SB, Caesar C, Roufail S, Achen MG, Stacker SA, Mercer AA (2003) Viral vascular endothelial growth factors vary extensively in amino acid sequence, receptor-binding specificities, and the ability to induce vascular permeability yet are uniformly active mitogens. J Biol Chem 278: 38004–38014
Savory LJ, Stacker SA, Fleming SB, Niven BE, Mercer AA (2000) Viral vascular endothelial growth factor plays a critical role in orf virus infection. J Virol 74: 10699–10706
Chang HW, Watson JC, Jacobs BL (1992) The E3L gene of vaccinia virus encodes an inhibitor of the interferon-induced, double-stranded RNA-dependent protein kinase. Proc Natl Acad Sci USA 89: 4825–4829
Vijaysri S, Talasela L, Mercer AA, McInnes CJ, Jacobs BL, Langland JO (2003) The Orf virus E3L homologue is able to complement deletion of the vaccinia virus E3L gene in vitro but not in vivo. Virology 314: 305–314
Kwon JA, Rich A (2005) Biological function of the vaccinia virus Z-DNA-bind.ing protein E3L: Gene transactivation and antiapoptotic activity in HeLa cells. Proc Natl Acad Sci USA 102: 12759–12764
Camus-Bouclainville C, Fiette L, Bouchiha S, Pignolet B, Counor D, Filipe C, Gelfi J, Messud-Petit F (2004) A virulence factor of myxoma virus colocalizes with NF-kappaB in the nucleus and interferes with inflammation. J Virol 78: 2510–2516
Johnston JB, Wang G, Barrett JW, Nazarian SH, Colwill K, Moran M, McFadden G (2005) Myxoma virus M-T5 protects infected cells from the stress of cell cycle arrest through its interaction with host cell cullin-1. J Virol 79: 10750–10763
Bos JD, Kapsenberg ML (1993) The skin immune system: progress in cutaneous biology. Immunol Today 14: 75–78
Becherel PA, LeGoff L, Frances C, Chosidow O, Guillosson JJ, Debre P, Mossalayi MD, Arock M (1997) Induction of IL-10 synthesis by human keratinocytes through CD23 ligation: a cyclic adenosine 3’,5’-monophosphate-dependent mechanism. J Immunol 159: 5761–5765
Garvey TL, Bertin J, Siegel RM, Wang GH, Lenardo J, Cohen JI (2002) Binding of FADD and caspase-8 to molluscum contagiosum virus MC159 v-FLIP is not sufficient for its antiapoptotic function. J Virol 76: 697–706
Garvey T, Bertin J, Siegel R, Lenardo M, Cohen J (2002) The death effector domains (DEDs) of the molluscum contagiosum virus MC159 v-FLIP protein are not functionally interchangeable with each other or with the DEDs of caspase-8. Virology 300: 217–225
Shisler JL, Moss B (2001) Molluscum contagiosum virus inhibitors of apoptosis: The MC159 v-FLIP protein blocks Fas-induced activation of procaspases and degradation of the related MC160 protein. Virology 282: 14–25
Thome M, Schneider P, Hofmann K, Fickenscher H, Meinl E, Neipel F, Mattmann C, Burns K, Bodmer J, Schroter M et al (1997) Viral FLICE-inhibitory proteins (FLIPs) prevent apoptosis induced by death receptors. Nature 386: 517–521
Quan LT, Caputo A, Bleackley RC, Pickup DJ, Salvesen GS (1995) Granzyme B is inhibited by the cowpox virus serpin cytokine response modifier A. J Biol Chem 270: 10377–10379
Ray CA, Black RA, Kronheim SR, Greenstreet TA, Sleath PR, Salvesen GS, Pickup DJ (1992) Viral inhibition of inflammation: cowpox virus encodes an inhibitor of the interleukin-1 beta converting enzyme. Cell 69: 597–604
Sen GC (2001) Viruses and interferons. Annu Rev Microbiol 55: 255–281
Johnston JB, McFadden G (2003) Poxvirus immunomodulatory strategies: current perspectives. J Virol 77: 6093–6100
Gil J, Esteban M (2000) Induction of apoptosis by the dsRNA-dependent protein kinase (PKR): mechanism of action. Apoptosis 5: 107–114
Xiang Y, Condit RC, Vijaysri S, Jacobs B, Williams BR, Silverman RH (2002) Blockade of interferon induction and action by the E3L double-stranded RNA binding proteins of vaccinia virus. J Virol 76: 5251–5259
Langland JO, Jacobs BL (2002) The role of the PKR-inhibitory genes, E3L and K3L, in determining vaccinia virus host range. Virology 299: 133–141
Huang H, Bi XG, Yuan JY, Xu SL, Guo XL, Xiang J (2005) Combined CD4+ Th1_effect and lymphotactin transgene expression enhance CD8+ Tc1_tumor localization and therapy. Gene Ther 12: 999–1010
McNiece I (1997) Interleukin-3 and the colony-stimulating factors. In: DG Remick, JS Friedland (eds): Cytokines in health and disease, 2nd edn. Marcel Dekker, Ann Arbor, 41–43
Kruse N, Weber O (2001) Selective induction of apoptosis in antigen-presenting cells in mice by Parapoxvirus ovis. J Virol 75: 4699–4704
Chang WL, Baumgarth N, Yu D, Barry PA (2004) Human cytomegalovirusencoded interleukin-10 homolog inhibits maturation of dendritic cells and alters their functionality. J Virol 78: 8720–8731
Buttner M (1993) Principles of paramunization. Option and limits in veterinary medicine. Comp Immunol Microbiol Infect Dis 16: 1–10
Fachinger V, Schlapp T, Saalmuller A (2000) Evidence for a parapox ovis virusassociated superantigen. Eur J Immunol 30: 2962–2971
Fachinger V, Schlapp T, Strube W, Schmeer N, Saalmuller A (2000) Poxvirusinduced immunostimulating effects on porcine leukocytes. J Virol 74: 7943–7951
Forster R, Wolf G, Mayr A (1994) Highly attenuated poxviruses induce functional priming of neutrophils in vitro. Arch Virol 136: 219–226
Mayr A, Buttner M, Wolf G, Meyer H, Czerny C (1989) Experimental detection of the paraspecific effects of purified and inactivated poxviruses. Zentralbl Veterinarmed B 36: 81–99
Weber O, Siegling A, Friebe A, Limmer A, Schlapp T, Knolle P, Mercer A, Schaller H, Volk HD (2003) Inactivated parapoxvirus ovis (Orf virus) has antiviral activity against hepatitis B virus and herpes simplex virus. J Gen Virol 84: 1843–1852
Henkel M, Planz O, Fischer T, Stitz L, Rziha HJ (2005) Prevention of virus persistence and protection against immunopathology after Borna disease virus infection of the brain by a novel Orf virus recombinant. J Virol 79: 314–325
Rziha H, Henkel M, Cottone R, Bauer B, Auge U, Gotz F, Pfaff E, Rottgen M, Dehio C, Buttner M (2000) Generation of recombinant parapoxviruses: non-essential genes suitable for insertion and expression of foreign genes. J Biotechnol 83: 137–145
Rziha HJ, Henkel M, Cottone R, Meyer M, Dehio C, Buttner M (1999) Parapoxviruses: potential alternative vectors for directing the immune response in permissive and non-permissive hosts. J Biotechnol 73: 235–242
Marsland BJ, Tisdall DJ, Heath DD, Mercer AA (2003) Construction of a recombinant orf virus that expresses an Echinococcus granulosus vaccine antigen from a novel genomic insertion site. Arch Virol 148: 555–562
Fischer T, Planz O, Stitz L, Rziha HJ (2003) Novel recombinant parapoxvirus vectors induce protective humoral and cellular immunity against lethal herpesvirus challenge infection in mice. J Virol 77: 9312–9323
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2007 Birkhäuser Verlag Basel/Switzerland
About this chapter
Cite this chapter
Fleming, S.B., Mercer, A.A. (2007). Genus Parapoxvirus . In: Mercer, A.A., Schmidt, A., Weber, O. (eds) Poxviruses. Birkhäuser Advances in Infectious Diseases. Birkhäuser Basel. https://doi.org/10.1007/978-3-7643-7557-7_7
Download citation
DOI: https://doi.org/10.1007/978-3-7643-7557-7_7
Publisher Name: Birkhäuser Basel
Print ISBN: 978-3-7643-7556-0
Online ISBN: 978-3-7643-7557-7
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)