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MHC class II DRB1 gene polymorphism in the pathogenesis of Maedi–Visna and pulmonary adenocarcinoma viral diseases in sheep

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Abstract

Ovine pulmonary adenocarcinoma (OPA) and Maedi–Visna (Maedi) are two chronic respiratory diseases of retroviral origin which occur worldwide. It is known that different host genetic factors influence the outcome of viral infections. To determine if variation in the Mhc-DRB1 gene was associated with progression to these ovine diseases, sheep lungs with and without OPA and Maedi lesions were collected. A sequence-based method was applied and 40 different alleles were detected in the sample analysed. In the allele-by-allele association analysis, allele DRB1*0325 had a significant association with susceptibility to Maedi (P = 0.045). For OPA, DRB1*0143 and DRB1*0323 were significantly associated with susceptibility (P = 0.024 and P = 0.029), and allele DRB1*0702 was significantly associated with resistance (P = 0.012). Based on these results, the Mhc-DRB1 alleles were classified by effect in three categories—susceptible (S), resistant (R) and neutral (N)—and animals were reassigned the genotypes as S/S, S/R, S/N, R/R, R/N and N/N. In a second analysis, penalised logistic regression models including a flock effect were run. In Maedi, significant association was detected for the N/S heterozygote (P = 0.0007), but not for the S/S homozygote, probably as a result of the low number of S/S animals. In OPA, association was detected for both the S/S and R/R homozygotes (P = 0.005 and P = 0.047). This allele grouping method may be applied in association studies with highly variable genes. This is the first study demonstrating significant associations between sheep Mhc-DRB1 alleles and susceptibility to OPA and Maedi. Therefore, both diseases are suitable candidates for more comprehensive genetic studies.

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References

  • Arrieta-Aguirre I, Garcia-Etxebarria K, Jugo BM (2006) Optimization of the MhcOvar-DRB1 gene typing. Tissue Antigens 67:222–228

    Article  CAS  PubMed  Google Scholar 

  • Berriatua E, Ávarez V, Extramiana B, González L, Daltabuit M, Juste R (2003) Transmission and control implications of seroconversion to Maedi–Visna virus in Basque dairy-sheep flocks. Prev Vet Med 60:265–279

    Article  PubMed  Google Scholar 

  • Cousens C, Thonur L, Imlach S, Crawford J, Sales J, Griffiths DJ (2009) Jaagsiekte sheep retrovirus is present at high concentration in lung fluid produced by ovine pulmonary adenocarcinoma-affected sheep and can survive for several weeks at ambient temperatures. Res Vet Sci 87:154–156

    Article  CAS  PubMed  Google Scholar 

  • Cutlip RC, Lehmkuhl HD, Brogden KA, Sacks JM (1986) Breed susceptibility to ovine progressive pneumonia (Maedi–Visna) virus. Vet Microbiol 12:283–288

    Article  CAS  PubMed  Google Scholar 

  • Daly AK, Day CP (2001) Candidate gene case-control association studies: advantages and potential pitfalls. Brit J Clin Pharmacol 52:489–499

    Article  CAS  Google Scholar 

  • Dalziel RG, Hopkins J, Watt NJ, Dutia BM, Clarke HAK, McConnell I (1991) Identification of a putative cellular receptor for the lentivirus visna virus. J Gen Virol 72:1905–1911

    Article  CAS  PubMed  Google Scholar 

  • Davies G, Genini S, Bishop SC, Giuffra E (2009) An assessment of opportunities to dissect host genetic variation in resistance to infectious diseases in livestock. Animal 3:415–436

    Article  Google Scholar 

  • De la Concha-Bermejillo A, Brodie SJ, Magnus-Corral S, Bowen RA, DeMartini JC (1995) Pathologic and serologic responses of isogeneic twin lambs to phenotypically distinct lentiviruses. J Acquir Immune Defic Syndr Hum Retrovirol 8:116–123

    PubMed  Google Scholar 

  • De las Heras M, González L, Sharp JM (2003) Pathology of ovine pulmonary adenocarcinoma. Curr Top Microbiol Immunol 275:25–54

    CAS  PubMed  Google Scholar 

  • DeMartini JC, de la Concha-Bermejillo A, Carlson JO, Bowen RA (2000) Diseases caused by Maedi–Visna and other lentiviruses. In: Axford RFE, Bishop SC, Nicholas FW, Owen JB (eds) Breeding for disease resistance in farm animals, 2nd edn. CAB, Oxon, pp 301–324

    Google Scholar 

  • Firth D (1993) Bias reduction of maximum likelihood estimates. Biometrika 80:27–38

    Article  Google Scholar 

  • Gail M, Williams R, Byar DP, Brown C (1976) How many controls? J Chron Dis 29:723

    Article  CAS  PubMed  Google Scholar 

  • García-Briones MM, Russell GC, Oliver RA, Tami C, Taboga O, Carrillo E, Palma EL, Sobrino F, Glass EJ (2000) Association of bovine DRB3 alleles with immune response to FMDV peptides and protection against viral challenge. Vaccine 19:1167–1171

    Article  PubMed  Google Scholar 

  • Gibert M, Balandraud N, Touinssi M, Mercier P, Roudier J, Reviron D (2003) Functional categorization of HLA-DRB1 alleles in rheumatoid arthritis: the protective effect. Hum Immunol 64:930–935

    Article  CAS  PubMed  Google Scholar 

  • González L, Juste RA, Cuervo LA, Idigoras I, Saez de Ocariz C (1993) Pathological and epidemiological aspects of the coexistence of Maedi–Visna and sheep pulmonary adenomatosis. Res Vet Sci 54:140–146

    PubMed  Google Scholar 

  • Grego E, De Meneghi D, Alvarez V, Benito AA, Minguijón E, Ortín A, Mattoni M, Moreno B, Pérez de Villarreal M, Alberti A, Capucchio MT, Caporale M, Juste R, Rosati S, De las Heras M (2008) Colostrum and milk can transmit jaagsiekte retrovirus to lambs. Vet Microbiol 130:247–257

    Article  PubMed  Google Scholar 

  • Heinze G, Ploner M (2003) Fixing the nonconvergence bug in logistic regression with SPLUS and SAS. Comput Meth Prog Bio 71:181–187

    Article  Google Scholar 

  • Herrmann-Hoesing LM, White SN, Mousel MR, Lewis GS, Knowles DP (2008) Ovine progressive pneumonia provirus levels associate with breed and Ovar-DRB1. Immunogenetics 60:749–758

    Article  PubMed  Google Scholar 

  • Hosmer DW, Lemeshow S (2000) Applied logistic regression. Wiley, New York

    Book  Google Scholar 

  • Houwers DJ (1990) Economic importance, epidemiology and control. In: Petursson G, Hoff-Jorgensen R (eds) Maedi–Visna and related diseases. Kluwer Academic, Boston, pp 83–117

    Google Scholar 

  • Houwers DJ, Visscher AH, Defise PR (1989) Importance of ewe lamb relationship and breed in the epidemiology of Maedi–Visna virus infections. Res Vet Sci 46:5–8

    CAS  PubMed  Google Scholar 

  • Jugo BM, Vicario A (2000) Single-strand conformational polymorphism and sequence polymorphism of Mhc-DRB in Latxa and Karrantzar sheep: implications for Caprinae phylogeny. Immunogenetics 51:887–897

    Article  CAS  PubMed  Google Scholar 

  • Jugo BM, Vicario A (2001) Lymphocyte antigens in sheep: linkage to the MHC class II DRB1 gene. Eur J Immunogenet 28:451–458

    Article  CAS  PubMed  Google Scholar 

  • Konnai S, Nagaoka Y, Takeshima S, Onuma M, Aida Y (2003) Sequences and diversity of 17 new Ovar-DRB1 alleles from three breeds of sheep. Eur J Immunogenet 30:275–282

    Article  CAS  PubMed  Google Scholar 

  • Leginagoikoa I, Juste R, Barandika J, Amorena B, De Andrés D, Luján L, Badiola J, Berriatua E (2006) Extensive rearing hinders Maedi–Visna virus (MVV) infection in sheep. Vet Res 37:767–778

    Article  PubMed  Google Scholar 

  • Miltiadou D, Law AS, Russell GC (2003) Establishment of a sequence-based typing system for BoLA-DRB3 exon 2. Tissue Antigens 62:55–65

    Article  CAS  PubMed  Google Scholar 

  • Nagaoka Y, Kabeya H, Onuma M, Kasai N, Okada K, Aida Y (1999) Ovine MHC class II DRB1 alleles associated with resistance or susceptibility to development of bovine leukemia virus-induced ovine lymphoma. Cancer Res 59:975–981

    CAS  PubMed  Google Scholar 

  • Palmarini M, Fan H (2001) Retrovirus-induced ovine pulmonary adenocarcinoma, an animal model for lung cancer. J Natl Cancer Inst 93:1603–1614

    Article  CAS  PubMed  Google Scholar 

  • Peterhans E, Greenland T, Badiola JJ, Harkiss G, Bertoni G, Amorena B, Eliaszewicz M, Juste RA, Krassnig R, Lafont JP, Lenihan P, Petursson G, Pritchard G, Thorley J, Vitu C, Mornex JF, Pépin M (2004) Routes of transmission and consequences of small ruminant lentiviruses (SRLVs) infection and eradication schemes. Vet Res 35:1–38

    Article  Google Scholar 

  • Petit RJ, El Mousadik A, Pons O (1998) Identifying populations for conservation on the basis of genetic markers. Conserv Biol 12:844–855

    Article  Google Scholar 

  • Raymond M, Rousset F (1995) GENEPOP Version 12: population genetics software for exact tests and ecumenicism. J Hered 86:248–249

    Google Scholar 

  • Reina R, Berriatua E, Luján L, Juste R, Sánchez A, de Andrés D, Amorena B (2008) Prevention strategies against small ruminant lentiviruses: an update. Vet J 182:31–37

    Article  PubMed  Google Scholar 

  • Ruff G, Regli JG, Lazary S (1993) Occurrence of caprine leucocyte class I and II antigens in Saanen goats affected by caprine arthritis (CAE). Eur J Immunogenet 20:285–288

    Article  CAS  PubMed  Google Scholar 

  • Sayers G, Good B, Hanrahan JP, Ryan M, Angles JM, Sweeney T (2005) Major histocompatibility complex DRB1 gene: its role in nematode resistance in Suffolk and Texel sheep breeds. Parasitology 131:403–409

    Article  CAS  PubMed  Google Scholar 

  • Singh I, McConnell I, Blacklaws B (2006) Immune response to individual Maedi–Visna virus gag antigens. J Virol 80:912–919

    Article  CAS  PubMed  Google Scholar 

  • Stear MJ, Belch A, Donskow-Schmelter K, Fitton LA, Innocent GT, Ishikane C, Mateus A, Murphy L, Rennie K, Smith A, Sayers G (2007) Detection of genes with moderate effects on disease resistance using ovine MHC and resistance to nematodes as an example. Vet Immunol Immunop 120:3–9

    Article  CAS  Google Scholar 

  • 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 83:1753–1757

    CAS  PubMed  Google Scholar 

  • Summers C, Norval M, De las Heras M, González L, Sharp JM, Woods GM (2005) An influx of macrophages is the predominant local immune response in ovine pulmonary adenocarcinoma. Vet Immunol Immunop 106:285–294

    Article  CAS  Google Scholar 

  • Traul DL, Li H, Dasgupta N, O'Toole D, Eldridge JA, Besser TE, Davies CJ (2007) Resistance to malignant catarrhal fever in American bison (Bison bison) is associated with MHC class IIa polymorphisms. Anim Genet 38:141–146

    Article  CAS  PubMed  Google Scholar 

  • Voigt K, Krämer U, Brügmann M, Dewar P, Sharp JM, Ganter M (2007) Eradication of ovine pulmonary adenocarcinoma by motherless rearing of lambs. Vet Rec 161:129–132

    CAS  PubMed  Google Scholar 

  • Voorter CEM, Lee KW, Smillie D, Tilanus MGJ, van den Berg-Loonen EM (2007) Sequence-based typing of HLA-DQA1: comprehensive approach showed molecular heterogeneity. Tissue Antigens 69(s1):76–81

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We acknowledge Dr. Josune Arranz, Felisa Arrese and Lourdes Mintegi for providing animals and data for the study and Adoración Cortés, Helena Camino and Lía Arana from the Veterinary Services and Auxiliary Team from MAFRIDO for providing samples and required information. We wish to thank two anonymous referees for their contribution to the improvement of the manuscript. This work was funded by a grant from the Instituto Nacional de Investigación y Tecnología Agraría y Alimentaria (INIA) RTA02-003-C2. A. Larruskain and K. García-Etxebarria are recipients of the University of the Basque Country (UPV/EHU) pre-doctoral grants. Esmeralda Minguijón’s salary is partially covered by the INIA program for incorporation for Ph.D. graduates into agricultural research centres.

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  1. Bernardino Moreno

    Present address: EXOPOL, 50840, San Mateo de Gallego, Spain

Authors and Affiliations

  1. Genetics, Physical Anthropology and Animal Physiology Department, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Bilbao, Spain

    Amaia Larruskain, Koldo García-Etxebarria & Begoña M. Jugo

  2. Animal Health Department, NEIKER-Tecnalia, 48160, Derio, Biscay, Spain

    Esmeralda Minguijón, Bernardino Moreno & Ramón A. Juste

  3. Applied Mathematics and Statistics and Operative Research, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Bilbao, Spain

    Inmaculada Arostegui

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  1. Amaia Larruskain
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Correspondence to Begoña M. Jugo.

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Larruskain, A., Minguijón, E., García-Etxebarria, K. et al. MHC class II DRB1 gene polymorphism in the pathogenesis of Maedi–Visna and pulmonary adenocarcinoma viral diseases in sheep. Immunogenetics 62, 75–83 (2010). https://doi.org/10.1007/s00251-009-0419-2

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