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Diagnosis and PrP genotype target of scrapie in clinically healthy sheep of Massese breed in the framework of a scrapie eradication programme

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Summary.

The application of a selective culling programme in two scrapie affected flocks of Massese breed sheep is described. The genetic susceptibility of this breed and the sensitivity of different diagnostic methods in the pre-clinical diagnosis of scrapie were also investigated. Overall, 2,068 clinically healthy sheep underwent PrP genotyping, providing the basis for selective culling. The prevalence of scrapie infection was investigated in susceptible sheep by two independent diagnostic methods. All the sheep older than 18 months (n = 620) were tested by Prionics® Check Western rapid test on the obex, with a prevalence of infection of 3.9%. Furthermore, 385 sheep underwent immunohistochemistry (IHC) on retropharyngeal lymph node (RPLN), with a prevalence of infection of 5.2%. Overall, 32 sheep were diagnosed with pre-clinical scrapie. Of these, 31 were positive by Western blot on the spleen, 29 by IHC on the RPLN and tonsil, 28 by IHC on the obex, 24 by rapid test, and only 18 by IHC on the third eyelid. All the scrapie positive sheep were of the ARQ/ARQ, ARQ/AHQ or ARQ/VRQ genotypes. No significant differences in scrapie prevalence were observed among these genotypes. The estimated risk of the three targeted alleles was also similar, suggesting that in this breed the VRQ allele was not at higher risk for scrapie, compared to the ARQ and AHQ alleles.

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References

  • C Acin I Martin-Burriel W Goldmann J Lyahyai M Monzon R Bolea A Smith C Rodellar JJ Badiola P Zaragoza (2004) ArticleTitlePrion protein gene polymorphisms in healthy and scrapie-affected Spanish sheep. J Gen Virol 85 2103–2110 Occurrence Handle10.1099/vir.0.80047-0 Occurrence Handle15218196

    Article  PubMed  Google Scholar 

  • PL Acutis L Sbaiz F Verburg MV Riina G Ru G Moda M Caramelli A Bossers (2004) ArticleTitleLow frequency of the scrapie resistance-associated allele and presence of lysine-171 allele of the prion protein gene in Italian Biellese ovine breed. J Gen Virol 85 3165–3172 Occurrence Handle10.1099/vir.0.80053-0 Occurrence Handle15448380

    Article  PubMed  Google Scholar 

  • U Agrimi G Ru F Cardone M Pocchiari M Caramelli (1999) ArticleTitleEpidemic of trasmissibile spongiform encephalopathy in sheep and goats in Italy. Lancet 353 560–561 Occurrence Handle10.1016/S0140-6736(98)04545-0

    Article  Google Scholar 

  • U Agrimi M Conte L Morelli MA Di Bari G Di Guardo C Ligios G Antonucci GM Aufiero N Pozzato F Mutinelli R Nonno G Vaccari (2003) ArticleTitleAnimal trasmissibile spongiform encephalopathies and genetics. Vet Res Commun 27 31–38 Occurrence Handle10.1023/B:VERC.0000014115.18327.26 Occurrence Handle14535366

    Article  PubMed  Google Scholar 

  • O Andreoletti P Berthon D Marc P Sarradin J Grosclaude L van Keulen F Schelcher J-M Elsen F Lantier (2000) ArticleTitleEarly accumulation of PrPSc in gut-associated lymphoid and nervous tissues of susceptible sheep from a Romanov flock with natural scrapie. J Gen Virol 81 3115–3126 Occurrence Handle11086143

    PubMed  Google Scholar 

  • TGM Baron J-Y Madec D Calavas Y Richard F Barillet (2000) ArticleTitleComparison of French natural scrapie isolates with bovine spongiform encephalopathy and experimental scrapie infected sheep. Neurosci Lett 284 175–178 Occurrence Handle10.1016/S0304-3940(00)01047-8 Occurrence Handle10773427

    Article  PubMed  Google Scholar 

  • M Baylis W Goldmann F Houston D Cairns A Chong A Ross A Smith N Hunter AR McLean (2002) ArticleTitleScrapie epidemic in a fully PrP-genotyped sheep flock. J Gen Virol 83 2907–2914 Occurrence Handle12388827

    PubMed  Google Scholar 

  • M Baylis C Chihota E Stevenson W Goldmann A Smith K Sivam S Tongue MB Gravenor (2004) ArticleTitleRisk of scrapie in British sheep of different prion protein genotype. J Gen Virol 85 2735–2740 Occurrence Handle10.1099/vir.0.79876-0 Occurrence Handle15302967

    Article  PubMed  Google Scholar 

  • M Baylis W Goldmann (2004) ArticleTitleThe genetics of scrapie in sheep and goats. Curr Mol Med 4 385–396 Occurrence Handle10.2174/1566524043360672 Occurrence Handle15354869

    Article  PubMed  Google Scholar 

  • M Beekes PA McBride E Bauldaf (1998) ArticleTitleCerebral targeting indicates vagal spread of infection in hamsters fed with scrapie. J Gen Virol 79 601–607 Occurrence Handle9519840

    PubMed  Google Scholar 

  • PBGM Belt IH Muileman BEC Schreuder J Bos-de Ruijter ALJ Gielkens MA Smits (1995) ArticleTitleIdentifications of five allelic variants of the sheep PrP gene and their association with natural scrapie. J Gen Virol 76 509–517 Occurrence Handle7897344

    PubMed  Google Scholar 

  • SL Benestad P Sarradin B Thu J Schonheit MA Tranulis B Bratberg (2003) ArticleTitleCases of scrapie with unusual features in Norway and designation of a new type, Nor98. Vet Rec 153 202–208 Occurrence Handle12956297

    PubMed  Google Scholar 

  • DC Bolton MP McKinley SB Prusiner (1982) ArticleTitleIdentification of a protein that purifies with the scrapie prion. Science 218 1309–1311 Occurrence Handle6815801

    PubMed  Google Scholar 

  • A Bossers BEC Schreuder ID Muileman PBGM Belt MA Smith (1996) ArticleTitlePrP genotype contributes to determining survival times of sheep with natural scrapie. J Gen Virol 77 2669–2673 Occurrence Handle8887505

    PubMed  Google Scholar 

  • C Clouscard P Beaudry JM Elsen D Milan M Dussaucy C Bounneau F Schelder J Chatelain JM Launay JL Laplance (1995) ArticleTitleDifferent allelic effects of the codon 136 and 171 of the prion protein gene in sheep with natural scrapie. J Gen Virol 76 2097–2101 Occurrence Handle7636494

    PubMed  Google Scholar 

  • GC Cravero F Guarda U Dotta R Guglielmino (1977) ArticleTitleLa scrapie in pecore di razza biellese. Prima segnalazione in Italia. La Clinica Veterinaria 100 1–5

    Google Scholar 

  • DEFRA (2001) National Scrapie Plan for Great Britain. Department of Environment, Food and Rural Affairs, pp. 28

  • J-M Elsen Y Amigues F Schelcher V Ducrocq O Andreoletti F Eychenne JV Tien Khang J-P Poivey F Lantier J-L Laplanche (1999) ArticleTitleGenetic susceptibility and trasmission factors in scrapie: detailed analysis of an epidemic in a closed flock of Romanov. Arch Virol 144 431–445 Occurrence Handle10.1007/s007050050516 Occurrence Handle10226611

    Article  PubMed  Google Scholar 

  • C Ersdal MJ Ulvund SL Benestad MA Tranulis (2003) ArticleTitleAccumulation of pathogenic prion protein (PrPSc) in nervous and lymphoid tissues of sheep with subclinical scrapie. Vet Pathol 40 164–174 Occurrence Handle10.1354/vp.40-2-164 Occurrence Handle12637756

    Article  PubMed  Google Scholar 

  • W Goldmann N Hunter JD Foster JM Salbaum K Beyreuther J Hope (1990) ArticleTitleTwo alleles of a neural protein gene linked to scrapie in sheep. Proc Natl Acad Sci USA 87 2476–2480 Occurrence Handle1969635

    PubMed  Google Scholar 

  • W Goldmann N Hunter G Smith J Foster J Hope (1994) ArticleTitlePrP genotype and agent effects in scrapie: change in allelic interaction with different isolates of agent in sheep, a natural host of scrapie. J Gen Virol 75 989–995 Occurrence Handle7909834

    PubMed  Google Scholar 

  • R Heggebø CM Press G Gunnes KI Lie MA Tranulis M Ulvund MH Groschup T Landsverk (2000) ArticleTitleDistribution of prion protein in the ileal Peyer’s patch of scrapie-free lambs and lambs naturally and experimentally exposed to the scrapie agent. J Gen Virol 81 2327–2337 Occurrence Handle10950992

    PubMed  Google Scholar 

  • R Heggebø CMcL Press G Gunnes MJ Ulvund MA Tranulis T Landsverk (2003) ArticleTitleDetection of PrPSc in lymphoid tissues of lambs experimentally exposed to the scrapie agent. J Comp Pathol 128 172–181 Occurrence Handle10.1053/jcpa.2002.0625 Occurrence Handle12634095

    Article  PubMed  Google Scholar 

  • AF Hill KCL Sidle S Joiner P Keyes TC Martin M Dawson J Collinge (1998) ArticleTitleMolecular screening of sheep for bovine spongiform encephalopathy. Neurosci Lett 255 159–162 Occurrence Handle10.1016/S0304-3940(98)00736-8 Occurrence Handle9832197

    Article  PubMed  Google Scholar 

  • N Hunter JD Foster W Goldmann MJ Stear J Hope C Bostock (1996) ArticleTitleNatural scrapie in a closed flock of Cheviot sheep occurs only in specific PrP genotypes. Arch Virol 141 809–824 Occurrence Handle10.1007/BF01718157 Occurrence Handle8678828

    Article  PubMed  Google Scholar 

  • N Hunter (1997) ArticleTitlePrP genetics in sheep and the implications for scrapie and BSE. Trend Microbiol 5 331–334 Occurrence Handle10.1016/S0966-842X(97)01081-0

    Article  Google Scholar 

  • N Hunter L Moore BD Hosie WS Dingwall A Greig (1997) ArticleTitleAssociation between natural scrapie and PrP genotype in a flock of Suffolk sheep in Scotland. Vet Rec 140 59–63 Occurrence Handle9023905

    PubMed  Google Scholar 

  • M Jeffrey I Begara-McGorum S Clark S Martin J Clark M Chaplin L Gonzalez (2002) ArticleTitleOccurrence and distribution of infection-specific PrP in tissues of clinical scrapie cases and cull sheep from scrapie-affected farms in Shetland. J Comp Pathol 127 264–273 Occurrence Handle10.1053/jcpa.2002.0592 Occurrence Handle12443734

    Article  PubMed  Google Scholar 

  • JL Laplanche J Chatelain D Westaway S Thomas M Dussaucy J Brugere-Picoux JM Launay (1993) ArticleTitlePrP polymorphisms associated with natural scrapie discovered by denaturing gradient gel electrophoresis. Genomics 15 30–37 Occurrence Handle10.1006/geno.1993.1006 Occurrence Handle8094373

    Article  PubMed  Google Scholar 

  • CI Lasmezas JP Deslys O Robain A Jaegly V Beringue JM Peyrin JG Fournier JJ Hauw J Rossier D Dormont (1996) ArticleTitleTrasmission of the BSE agent to mice in absence of detectable abnormal prion protein. Science 275 402–405 Occurrence Handle10.1126/science.275.5298.402

    Article  Google Scholar 

  • T Moum I Olsaker P Hopp T Moldal M Valheim T Moum SL Benestad (2005) ArticleTitlePolymorphisms at codons 141 and 154 in the ovine prion protein gene are associated with scrapie Nor98 cases. J Gen Virol 86 231–235 Occurrence Handle10.1099/vir.0.80437-0 Occurrence Handle15604451

    Article  PubMed  Google Scholar 

  • F Mutinelli GM Aufiero N Pozzato S Marangon U Agrimi G Vaccari G Vincenzi (2003) ArticleTitleEradication of scrapie in a Massese sheep flock by PrP allele selection. Vet Rec 152 60 Occurrence Handle12553587

    PubMed  Google Scholar 

  • R Nonno E Esposito G Vaccari M Conte S Marcon M Di Bari C Ligios G Di Guardo U Agrimi (2003) ArticleTitleMolecular analysis of cases of Italian sheep scrapie and comparison with cases of bovine spongiform encephalopathy (BSE) and experimental BSE in sheep. J Clin Microbiol 41 4127–4133 Occurrence Handle10.1128/JCM.41.9.4127-4133.2003 Occurrence Handle12958236

    Article  PubMed  Google Scholar 

  • E O’Doherty A Healy M Aherne JP Hanrahan E Weavers M Doherty JF Roche M Gunn T Sweeney (2002) ArticleTitlePrion protein (PrP) gene polymorphisms associated with natural scrapie cases and their flock-mates in Ireland. Res Vet Sci 73 243–250 Occurrence Handle10.1016/S0034-5288(02)00073-5 Occurrence Handle12443681

    Article  PubMed  Google Scholar 

  • KI O’Rourke GR Holyoak WW Clark JR Mickelson S Wang RP Melco TE Besser WC Foote (1997) ArticleTitlePrP genotypes and experimental scrapie in orally inoculated Suffolk sheep in the United States. J Gen Virol 78 975–978 Occurrence Handle9129673

    PubMed  Google Scholar 

  • KI O’Rourke TV Baszler SM Parish DP Knowles (1998) ArticleTitlePreclinical detection of PrP nictitating membrane lymphoid tissue of sheep. Vet Rec 142 489–491 Occurrence Handle9612916

    PubMed  Google Scholar 

  • KI O’Rourke TV Baszler TE Besser JM Miller RC Cutlip GAH Wells SJ Ryder SM Parish AN Hamir NE Cockett A Jenny DP Knowles (2000) ArticleTitlePreclinical diagnosis of scrapie by immunohistochemistry of third eyelid lymphoid tissue. J Clin Microbiol 38 3254–3259 Occurrence Handle10970367

    PubMed  Google Scholar 

  • IH Pattison MN Hoare JN Jebbett WA Watson (1972) ArticleTitleSpread of scrapie to sheep and goats by oral dosing with foetal membranes from scrapie-affected sheep. Vet Rec 90 465–468 Occurrence Handle4625088

    PubMed  Google Scholar 

  • SB Prusiner (1982) ArticleTitleNovel proteinaceous infectious particles cause scrapie. Science 216 136–144 Occurrence Handle6801762

    PubMed  Google Scholar 

  • O Schaller R Fatzer M Stack J Clark W Cooley K Biffiger S Egli M Doherr M Vandevelde D Heim B Oesch M Moser (1999) ArticleTitleValidation of a Western immunoblotting procedure for bovine PrPSc detection and its use as a rapid survillance method for the diagnosis of bovine spongiform encephalopathy (BSE). Acta Neuropathol 98 437–443 Occurrence Handle10.1007/s004010051106 Occurrence Handle10541864

    Article  PubMed  Google Scholar 

  • BEC Schreuder LJM van Keulen MEW Vromans JPM Langeveld MA Smits (1998) ArticleTitleTonsillar biopsy and PrPSc detection in the preclinical diagnosis of scrapie. Vet Rec 142 564–568 Occurrence Handle9634704

    PubMed  Google Scholar 

  • SEAC (2003) Summary of the results of scrapie surveillance in sheep in Great Britain. Paper No.: SEAC 78/4. www.seac.gov.uk/papers/seac78_4.pdf (accessed December 3rd, 2004)

  • TR Spraker KI O’Rourke A Balachandran RR Zink BA Cummings MW Miller BE Powers (2002) ArticleTitleValidation of monoclonal antibody F99/97.6.1 for immunohistochemical staining of brain and tonsil in mule deer (Odocoileus hemionus) with chronic wasting disease. J Vet Diagn Invest 14 3–7 Occurrence Handle12680636

    PubMed  Google Scholar 

  • MJ Stack MJ Chaplin J Clark (2002) ArticleTitleDifferentiation of prion protein glycoforms from naturally occurring sheep scrapie, sheep-passaged scrapie strain (CH1641 and SSBP1), bovine spongiform encephalopathy (BSE) cases and Romney and Cheviot breed sheep experimentally inoculated with BSE using two monoclonal antibodies. Acta Neuropathol 104 279–286 Occurrence Handle12172914

    PubMed  Google Scholar 

  • S Thorgeirsdottir G Georgsson E Reynisson S Sigurdarson A Palsdottir (2002) ArticleTitleSearch for healthy carriers of scrapie: an assessment of subclinical infection of sheep in an Icelandic scrapie flock by three diagnostic methods and correlation with PrP genotypes. Arch Virol 147 709–722 Occurrence Handle10.1007/s007050200020 Occurrence Handle12038682

    Article  PubMed  Google Scholar 

  • MA Tranulis A Osland B Bratberg MJ Ulvund (1999) ArticleTitlePrion protein gene polymorphisms in sheep with natural scrapie and healthy controls in Norway. J Gen Virol 80 1073–1077 Occurrence Handle10211978

    PubMed  Google Scholar 

  • MA Tranulis (2002) ArticleTitleInfluence of the prion protein gene, Prnp, on scrapie susceptibility in sheep. APMIS 110 33–43 Occurrence Handle10.1034/j.1600-0463.2002.100105.x Occurrence Handle12064254

    Article  PubMed  Google Scholar 

  • G Vaccari R Petraroli U Agrimi C Eleni MG Perfetti MA Di Bari L Morelli C Ligios L Busani R Nonno G Di Guardo (2001) ArticleTitlePrP genotype in Sarda breed sheep and its relevance to scrapie. Arch Virol 146 2029–2037 Occurrence Handle10.1007/s007050170050 Occurrence Handle11722022

    Article  PubMed  Google Scholar 

  • LJM van Keulen BEC Schreuder RH Meolen G Mooij-Harkes MEW Vromans JPM Langeveld (1996) ArticleTitleImmunohistochemical detection of prion protein in lymphoid tissues of sheep with natural scrapie. J Clin Microbiol 34 1228–1231 Occurrence Handle8727908

    PubMed  Google Scholar 

  • LJM van Keulen BEC Schreuder MEW Vromans JPM Langeveld MA Smits (2000) ArticleTitlePathogenesis of natural scrapie in sheep. Arch Virol Suppl 16 57–71 Occurrence Handle11214935

    PubMed  Google Scholar 

  • LJM van Keulen MEW Vromans FG van Zijderveld (2002) ArticleTitleEarly and late pathogenesis of natural scrapie infection in sheep. APMIS 110 23–32 Occurrence Handle10.1034/j.1600-0463.2002.100104.x Occurrence Handle12064252

    Article  PubMed  Google Scholar 

  • D Westaway V Zuliani CM Cooper M Da Costa S Neuman AL Jenny L Detwiler SB Prusiner (1994) ArticleTitleHomozygousity for prion protein alleles encoding glutamine-171 renders sheep susceptible to natural scrapie. Genes Dev 8 959–969 Occurrence Handle7926780

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Histopathology Department, Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro (PD), Italy

    M. Vascellari, G. M. Aufiero, L. Basilicata, C. Falcaro & F. Mutinelli

  2. Department of Food Safety and Veterinary Public Health, Istituto Superiore di Sanità, Roma, Italy

    R. Nonno, U. Agrimi, G. Vaccari & S. Marcon

  3. Epidemiology Unit, Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro (PD), Italy

    M. Mancin

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  1. M. Vascellari
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  2. G. M. Aufiero
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  3. R. Nonno
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  4. U. Agrimi
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  5. G. Vaccari
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  6. L. Basilicata
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  7. C. Falcaro
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  8. M. Mancin
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  9. S. Marcon
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  10. F. Mutinelli
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Vascellari, M., Aufiero, G., Nonno, R. et al. Diagnosis and PrP genotype target of scrapie in clinically healthy sheep of Massese breed in the framework of a scrapie eradication programme. Arch Virol 150, 1959–1976 (2005). https://doi.org/10.1007/s00705-005-0564-3

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  • DOI: https://doi.org/10.1007/s00705-005-0564-3

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