Natural History of JSRV in Sheep

  • J. M. Sharp
  • J. C. DeMartini
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 275)


Ovine pulmonary adenocarcinoma (OPA) is a contagious lung tumour of sheep and, rarely, goats that arises from two types of secretory epithelial cell that retain their luxury function of surfactant synthesis and secretion. It is classified as a low-grade adenocarcinoma and is viewed as a good model for epithelial neoplasia because of its morphological resemblance to the human lung tumour, bronchioloalveolar adenocarcinoma. OPA is present in most of the sheep rearing areas of the globe and, in affected flocks, tumours are present in a high proportion of sheep. OPA is associated with the ovine retrovirus, jaagsiekte sheep retrovirus (JSRV), and is transmissible only with inocula that contain JSRV. All sheep contain JSRV-related endogenous viruses, but JSRV is an exogenous virus that is associated exclusively with OPA. JSRV is detected consistently in the lung fluid, tumour and lymphoid tissues of sheep affected by both natural and experimental OPA or unaffected in-contact flockmates and never in sheep from unaffected flocks with no history of the tumour. JSRV replicates principally in the epithelial tumour cells, but also establishes a disseminated infection of several lymphoid cell types, including peripheral blood leukocytes (PBLs). Longitudinal studies in flocks with endemic OPA have revealed JSRV in PBLs before the onset of clinical OPA and even in the absence of discernible lung tumour. The prevalence of JSRV infection is 40%–80%, although only 30% of sheep appear to develop OPA lesions. A unique feature of OPA is the absence of a specific humoral immune response to JSRV, despite the highly productive infection in the lungs and the disseminated lymphoid infection. This feature is associated with reduced responsiveness to some mitogens, although the phenotypic profile of the peripheral blood remains unaltered. The reduced response is an early and sustained event during infection and may indicate that the failure of infected sheep to produce specific antibodies to JSRV is a direct consequence of infection.


Long Terminal Repeat Clara Cell Lung Fluid Infected Sheep ATII Cell 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bastianello S (1982) A survey on neoplasia in domestic species over a 40 Year period from 1935 to 1974 in the Republic of South Africa. II. Tumours occurring in sheep. Onderstepoort J Vet Res 49:205–209PubMedGoogle Scholar
  2. Bai J, Payne LN, Skinner M (1995) HPRS-103 (exogenous avian leukosis virus, subgoup J) has an env gene related to those of endogenous elements EAV-0 and E51 and an E element found previously only in sarcoma viruses. J Virol 69:779–784PubMedGoogle Scholar
  3. Bai J, Zhu R-Y, Stedman K, Cousens C, Carlson J, Sharp JM, DeMartini JC (1996) Unique long terminal repeat U3 sequences distinguish exogenous jaagsiekte sheep retroviruses associated with ovine pulmonary carcinoma from endogenous loci in the sheep genome. J Virol 70:3159–3168PubMedGoogle Scholar
  4. Bai J, Bishop JV, Carlson JO, DeMartini JC (1999) Sequence comparison of JSRV with endogenous proviruses: envelope genotypes and a novel ORF with similarity to a G protein coupled receptor. Virol 258:333–343CrossRefGoogle Scholar
  5. Cutlip RC, Young S (1982) Sheep pulmonary adenomatosis (Jaagsiekte) in the United States. Am J Vet Res 43:2108–2113PubMedGoogle Scholar
  6. Dalefield RR, Alley MR (1988) An ovine pulmonary tumour of alveolar epithelial type II cells. N Z Vet J 36:25–27PubMedCrossRefGoogle Scholar
  7. Dawson M, Done SH, Venables C, Jenkins CE (1990) Maedi-visna and sheep pulmonary adenomatosis: a study of concurrent infection. Br Vet J 146:531–533PubMedCrossRefGoogle Scholar
  8. De las Heras M, Hasleton P, Larson E, Wagner M, Minguijon E, Egan J, Dewar P, Ortin A, Gimenez-Mas JA, Gonzalez L, Palmarini M, Dalziel R, Sharp JM (2000) Human bronchioloalveolar cell carcinoma contains a protein related immunologically to the capsid protein of jaasiekte sheep retrovirus. Eur Resp J 15: 330–332CrossRefGoogle Scholar
  9. DeMartini JC, Rosadio RH, Lairmore MD (1988) The etiology and pathogenesis of ovine pulmonary carcinoma (sheep pulmonary adenomatosis). Vet Microbiol 17: 219–236PubMedCrossRefGoogle Scholar
  10. DeMartini JC, Rosadio RH, Sharp JM, Russell HI, Lairmore MD (1987) Experimental coinduction of type D retrovirus-associated pulmonary carcinoma and lentivirus-associated lymphoid interstitial pneumonia. J Natl Cancer Inst 79: 167–177PubMedGoogle Scholar
  11. DeMartini JC, York DF (1997) Retrovirus-associated neoplasms of the respiratory system of sheep and goats. Ovine pulmonary carcinoma and enzootic nasal tumor. Vet Clin North Am Food Anim Pract 13:55–70PubMedGoogle Scholar
  12. Dungal N (1949) Experiments with jaagsiekte. Am J Pathol 22:737–759Google Scholar
  13. Dykes JR, M’Fadyean J (1888) Lung disease in sheep caused by Strongylus rufescens. J Comp Path Therap 1:139–144CrossRefGoogle Scholar
  14. García-Goti M (1999) Estudios sobre la patogenia y diagnóstico de la adenomatosis pulmonar ovina. PhD Thesis. University of ZaragozaGoogle Scholar
  15. García-Goti M, González L, Cousens C, Cortabarria N, Extramiana AB, Minguijón E, Ortín A, Dde las Heras M, Sharp JM (2000) Sheep pulmonary adenomatosis: characterization of two pathological forms associated with jaagsiekte retrovirus. J Comp Pathol 122:55–65PubMedCrossRefGoogle Scholar
  16. Golovkina TV, Jaffe AB, Ross SR (1994) Coexpression of exogenous and endogenous mouse mammary tumour virus RNA in vivo results in viral recombination and broadens the virus host range. J Virol 68:5019–5026PubMedGoogle Scholar
  17. González L, García-Goti M, Cousens C, Dewar P, Cortabarría N, Extramiana B, Ortín A, De las Heras M, Sharp JM (2001) Jaagsiekte sheep retrovirus can be detected in the peripheral blood during the preclinical period of sheep pulmonary adenomatosis, J Gen Virol 82:1355–1358PubMedGoogle Scholar
  18. He Y, Hecht SJ, DeMartini JC (1992) Evidence for retroviral capsid and nucleocapsid antigens in ovine pulmonary carcinoma. Virus Res 25:159–167PubMedCrossRefGoogle Scholar
  19. Hecht S, Stedman K, Carlson J, DeMartini JC (1996) Distribution of endogenous type B and D sequences in ungulates and other mammals. Proc Natl Acad of Science USA 93:3297–3302CrossRefGoogle Scholar
  20. Herring AJ, Sharp JM, Scott FMM, Angus KW (1983) Further evidence for a retrovirus as the aetiological agent of sheep pulmonary adenomatosis (jaagsiekte). Vet Microbiol 8:237–249PubMedCrossRefGoogle Scholar
  21. Holland M, Palmarini M, Garcia-Goti M, Gonzalez L, McKendrick L, De LAS Heras M, Sharp JM (1999) Jaagsiekte retrovirus is widely distributed both in T and B lymphocytes and in mononuclear phagocytes of sheep with naturally and experimentally acquired pulmonary adenomatosis. J Virol 73:4004–4008PubMedGoogle Scholar
  22. Hooper PT, Ellard KA (1995) A pulmonary adenoma in an Australian sheep. Aust Vet J 72:477PubMedCrossRefGoogle Scholar
  23. Houwers DJ, Terpstra C (1984) Sheep pulmonary adenomatosis. Vet Rec 114:23PubMedCrossRefGoogle Scholar
  24. Hunter AR, Munro R (1983) The diagnosis, occurrence and distribution of sheep pulmonary adenomatosis in Scotland 1975 to 1981. Brit Vet J 139:153–164Google Scholar
  25. Jassim FA (1988) Identification and characterisation of transformed cells in jaagsiekte, a contagious lung tumour of sheep. PhD Thesis. University of EdinburghGoogle Scholar
  26. Kajikawa O, Dahlberg JE, Rosadio RH, DeMartini JC (1990) Detection and quantitation of a type D retrovirus gag protein in ovine pulmonary carcinoma (sheep pulmonary adenomatosis) by means of a competition radioimmunoassay. Vet Microbiol 25:17–28PubMedCrossRefGoogle Scholar
  27. Kwang J, Keen J, Rosati S, Tolari F (1995) Development and application of an antibody ELISA for the marker protein of ovine pulmonary carcinoma. Vet Immunol Immunopathol 47:323–331PubMedCrossRefGoogle Scholar
  28. Maeda N, Palmarini M, Murgia C, Fan H (2001) Direct transformation of rodent fibroblasts by jaagsiekte sheep retrovirus DNA. Proc Natl Acad Science USA 98: 4449–4454CrossRefGoogle Scholar
  29. Martin WB, Scott FMM, Sharp JM, Angus KW, Norval M (1976) The experimental production of sheep pulmonary adenomatosis (Jaagsiekte). Nature, London 264:183–185CrossRefGoogle Scholar
  30. Myer MS, Huchzermeyer HFAK, York DF, Hunter P, Verwoerd DW, Garnett HM (1988) The possible involvement of immunosuppression caused by a lentivirus in the aetiology of jaagsiekte and pasteurellosis in sheep. Onderstepoort J Vet Res 55:127–133PubMedGoogle Scholar
  31. Ortin A, Minguijon E, Dewar P, Garcia M, Ferrer LM, Palmarini M, Gonzalez L, Sharp JM, De LAS Heras M (1998) Lack of a specific immune response against a recombinant capsid protein of Jaagsiekte sheep retrovirus in sheep and goats nat-76 J. M. Sharp and J. C. DeMartini urally affected by enzootic nasal tumour or sheep pulmonary adenomatosis. Vet Immunol Immunopathol 61:229–237PubMedCrossRefGoogle Scholar
  32. Palmarini M, Dewar P, De LAS Heras M, Inglis NF, Dalziel RG, Sharp JM (1995) Epithelial tumour cells in the lungs of sheep with pulmonary adenomatosis are major sites of replication for Jaagsiekte retrovirus. J Gen Virol 76:2731–2737PubMedCrossRefGoogle Scholar
  33. Palmarini M, Cousens C, Dalziel RG, Bai J, Stedman K, DeMartini JC, Sharp JM (1996a) The exogenous form of Jaagsiekte retrovirus (JSRV) is specifically associated with a contagious lung cancer of sheep. J Virol 70:1618–1623PubMedGoogle Scholar
  34. Palmarini M, Holland MJ, Cousens C, Dalziel RG, Sharp JM (1996b) Jaagsiekte retrovirus (JSRV) establishes a disseminated infection of the lymphoid tissues in sheep affected by pulmonary adenomatosis. J Gen Virol 77:2991–2998PubMedCrossRefGoogle Scholar
  35. Palmarini M, Maeda N, Murgia C, De-Fraja C, Hofacre A, Fan H (2001) A phosphatidylinositol-3-kinase (PI3-K) docking site in the cytoplasmic tail of the jaagsiekte sheep retrovirus transmembrane protein is essential for envelopeinduced transformation of NIH 3T3 cells. J Virol 75:11002–11009PubMedCrossRefGoogle Scholar
  36. Palmarini M, Fan H (2001) Retrovirus-induced ovine pulmonary adenocarcinoma, an animal model for lung cancer. J Natl Cancer Inst 93:1603–1614PubMedCrossRefGoogle Scholar
  37. Pálsson PA: Maedi/visna of sheep in Iceland: Introduction of the disease to Iceland, clinical features, control measures, and eradication. In Sharp M, Hoff-Jorgensen R (eds): Slow Viruses in Sheep, Goats, and Cattle. Brussels, Commission of the European Communities 1985, pp 3–19Google Scholar
  38. Payne A, York DF, Dde Villiers EM, Verwoerd DW, Querat G, Barban V, Sauze N, Vigne R (1986) Isolation and identification of a South African lentivirus from jaagsiekte lungs. Onderstepoort J Vet Res 53:55–62PubMedGoogle Scholar
  39. Perk K, Hod I (1982) Sheep lung carcinoma: an epidemic analogue of a human neoplasm. J Natl Cancer Inst 69:747–750PubMedGoogle Scholar
  40. Platt J, Villafane F, Kraipowich N, DeMartini JC (2002) Alveolar type II cells expressing jaagsiekte sheep retrovirus capsid protein and surfactant proteins are the predominant neoplastic cell type in ovine pulmonary adenocarcinoma. Vet Pathol 39:341–352PubMedCrossRefGoogle Scholar
  41. Rai SK, Duh FM, Vigdorovich V, Danilkovitch-Miagkova A, Lerman MI, Miller AD (2001) Candidate tumour suppressor HYAL2 is a glycosylphospatidylinositol (GPI)-anchored cell-surface receptor for Jaagsiekte sheep retrovirus, the envelope protein of which mediates oncogenic transformation. Proc Natl Acad Science USA 98:4443–4448CrossRefGoogle Scholar
  42. Rajya BS, Singh CM (1964) The pathology of pneumonia and associated respiratory disease of sheep and goats. 1. Occurrence of jaagsiekte and maedi in sheep and goats in India. Am J Vet Res 25:61–67PubMedGoogle Scholar
  43. Roche S, Koegl M, Courtneidge SA (1994) The phosphatidylinositol 3-kinase a is required for DNA synthesis induced by some, but not all, growth factors. Proc Natl Acad Science USA 91:9185–9189CrossRefGoogle Scholar
  44. Rosadio R, Sharp JM (1992) Leukocyte frequency alterations in sheep with naturally and experimentally-induced lung cancer. Vet Med 9:49–51Google Scholar
  45. Rosadio RH, Lairmore MD, Russell HI, DeMartini JC (1988) Retrovirus-associated ovine pulmonary carcinoma (sheep pulmonary adenomatosis) and lymphoid interstitial pneumonia. I. Lesion development and age susceptibility. Vet Pathol 25: 475–483PubMedCrossRefGoogle Scholar
  46. Rosadio RH, Sharp JM, Lairmore MD, Dahlberg JE, DeMartini JC (1987) Lesions and retroviruses associated with naturally occurring ovine pulmonary carcinoma (sheep pulmonary adenomatosis). Vet Pathol 25:58–66CrossRefGoogle Scholar
  47. Rosati S, Pittau M, Alberti A, Pozzi S, York DF, Sharp JM, Palmarini M (2000) An accessory open reading frame (orf-x) of jaagsiekte sheep retrovirus is conserved between different virus isolates. Virus Res 66:109–116PubMedCrossRefGoogle Scholar
  48. Sanna MP, Sanna E, De las Heras M, Leoni A, Nieddu AM, Pirino S, Sharp JM, Palmarini M (2001) Jaagsiekte sheep retrovirus is associated with ovine pulmonary carcinoma in Sardinian moufflons. J Comp Pathol 125:145–152PubMedCrossRefGoogle Scholar
  49. Sharp JM (1987) Sheep pulmonary adenomatosis: a contagious tumour and its cause. Cancer Surv 6:73–83PubMedGoogle Scholar
  50. Sharp JM, De Las Heras M (2000) Contagious respiratory tumours. In: Diseases of Sheep, 3rd edition, ed.Martin and Aitken, pp 181–186Google Scholar
  51. Sharp JM, Herring AJ (1983) Sheep pulmonary adenomatosis: demonstration of a protein which cross-reacts with the major core proteins of Mason-Pfizer monkey virus and mouse mammary tumour virus. J Gen Virol 64:2323–2327PubMedCrossRefGoogle Scholar
  52. Sharp JM, Angus KW, Gray EW, Scott FMM (1983) Rapid transmission of sheep pulmonary adenomatosis (jaagsiekte) in young lambs. Arch Virol 78:89–95PubMedCrossRefGoogle Scholar
  53. Sharp JM, Angus KW, Jassim FA, et al (1986) Experimental transmission of sheep pulmonary adenomatosis to a goat. Vet Rec 19:245CrossRefGoogle Scholar
  54. Snyder SP, DeMartini JC, Ameghino E, Caletti E (1983) Coexistence of pulmonary adenomatosis and progressive pneumonia in sheep in the Central Sierra of Peru. Am J Vet Res 44:1334–1338PubMedGoogle Scholar
  55. Stefanou D, Tsangaris TH, Lekkas ST (1975) Pulmonary adenomatosis in goats in the district of Pieria (Greece). In: 20th World Vterinary Congress, Thessaloniki, Greece. Summaries, pp 495–496Google Scholar
  56. Stevenson RG, Finley GG, Long JR, Rehmtulla AJ (1982) Pulmonary adenomatosis (jaagsiekte) of sheep in Canada. Can Vet J 23:147–152PubMedGoogle Scholar
  57. Stoye JP, Moroni C, Coffin JM (1991) Virological events leading to spontaneous AKR thymomas. J Virol 65:1273–1285PubMedGoogle Scholar
  58. Summers C, Neill W, Dewar P, Gonzalez L, Van der Molen R, Norval M, Sharp JM (2002) Systemic immune responses following infection with jaagsiekte sheep retrovirus and in the terminal stages of ovine pulmonary adenocarcinoma. J Gen Virol 83:1753–1757PubMedGoogle Scholar
  59. Tustin RC (1969) Ovine jaagsiekte. J S Afr Vet Med Assoc 40:3–23Google Scholar
  60. Tustin RC, Williamson A, York DF et al. (1988) Experimental transmission of jaagsiekte (ovine pulmonary adenomatosis) to goats. Onderstepoort J Vet Res 55: 27–32PubMedGoogle Scholar
  61. Verwoerd DW, Tustin RC, Payne AL (1985) Jaagsiekte: An infectious pulmonary adenomatosis of sheep. In: Comparative Pathobiology of Viral Diseases, Olsen, Krakowka S, Blackslee JR (eds) pp 53–76. CRC Press, Inc.: Boca RatonGoogle Scholar
  62. Verwoerd DW, Mayer-Scharrer E, Du Plessis JL (1977) Transplantation of cultured jaagsiekte (sheep pulmonary adenomatosis) cells into athymic nude mice. Onderstepoort J Vet Res 44:271–274PubMedGoogle Scholar
  63. Verwoerd DW (1990) Jaagsiekte (ovine pulmonary adenomatosis) virus. In: Dinta Z and Morein B (eds), Virus infections of ruminants. Elsevier, pp 453–462Google Scholar
  64. Wandera JG (1968) Experimental transmission of sheep pulmonary adenomatosis (jaagsiekte). Vet Rec 83:478–482PubMedCrossRefGoogle Scholar
  65. Weiss R, Teich N, Varmus H, Coffin J (eds) (1985) RNA Tumour Viruses. Cold Spring Harbor LaboratoryGoogle Scholar
  66. York DF, Vigne R, Verwoerd DW and Querat G (1992) Nucleotide sequence of the jaagsiekte retrovirus, an exogenous and endogenous type D and B retrovirus of sheep and goats. J Virol 66:4930–4939PubMedGoogle Scholar
  67. Zimber A, Perk K, Hod I et al (1984) Heterotransplantation of experimentally — induced sheep lung adenomatosis into nude mice. Res Vet Sci 36:122–124PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2003

Authors and Affiliations

  • J. M. Sharp
    • 1
  • J. C. DeMartini
    • 2
  1. 1.Moredun Research InstitutePenicuikUK
  2. 2.Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical SciencesColorado State UniversityFort CollinsUSA

Personalised recommendations