Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Archives of Virology
Published in: Archives of Virology 4/2008

01-04-2008 | Original Article

High incidence of subclinical infection of lymphoid tissues in scrapie-affected sheep flocks

Authors: Gudmundur Georgsson, Jona Adalheidur Adolfsdottir, Astridur Palsdottir, Einar Jorundsson, Sigurdur Sigurdarson, Stefania Thorgeirsdottir

Published in: Archives of Virology | Issue 4/2008

Login to get access

Abstract

Prion diseases are characterized by a long incubation period. In scrapie, sheep may incubate and spread the infection for several years before clinical signs evolve. We have previously studied the occurrence of subclincal infection in the brain. Now, we have studied the occurrence of subclinical infection in the brain and several lymphoid tissues in two scrapie-affected Icelandic sheep flocks by immunohistochemistry for PrPSc, a molecular marker for infectivity, and correlated this with results of PrP genotyping. At culling, one flock had one confirmed scrapie case, while the other flock had two. Analysis of 106 asymptomatic sheep by immunostaining for PrPSc revealed that the incidence of subclinical infection was 58.3% in one flock and 42.5% in the other. PrPSc was only detected in lymphoid tissues. The youngest positive sheep were 4 months old. PrP genotyping showed that over 90% of the sheep were of a genotype which is moderately sensitive to infection and may delay neuroinvasion. Our results show that asymptomatic sheep may spread the infection during the long incubation period of several years, which constitutes an important obstacle in the eradication of scrapie. Our findings indicate that contamination of the environment plays an important part in sustaining the infection.
Literature
1.
Andréoletti O, Berthon P, Marc D, Sarradin P, Grosclaude J, van Keulen L, Schelcher F, Elsen J-M, Lantier F (2000) Early accumulation of PrPSc in gut-associated lymphoid and nervous tissue of susceptible sheep from a Romanov flock with natural scrapie. J Gen Virol 81:3115–3126PubMed
2.
Andréoletti O, Lacroux C, Chabert A, Monnereau L, Tabouret G, Lantier F, Berthon P, Eychenne F, Lafond-Benestad S, Elsen J-M, Schelcher F (2002) PrPSc accumulation in placentas of ewes exposed to natural scrapie: influence of foetal PrP genotype and effect on ewe-to-lamb transmission. J Gen Virol 83:2607–2616PubMed
3.
Belt PBGM, Muileman IH, Schreuder BEC, Bos-de Ruiter J, Gielkens ALJ, Smits MA (1995) Identification of five allelic variants of the sheep PrP gene and their association with natural scrapie. J Gen Virol 76:509–517PubMed
4.
Bolton DC, McKinley MP, Prusiner SB (1982) Identification of a protein that purifies with the scrapie prion. Science 218:1309–1311PubMedCrossRef
5.
Brown KL, Stewart K, Ritchie DL, Mabbott NA, Williams A, Fraser H, Morrison WI, Bruce ME (1999) Scrapie replication in lymphoid tissues depends on prion protein-expressing follicular dendritic cells. Nat Med 5:1308–1312PubMedCrossRef
6.
Bruce ME, Brown KL, Mabbott NA, Farquhar CF, Jeffrey M (2000) Follicular dendritic cells in TSE pathogenesis. Immunol Today 21:442–446PubMedCrossRef
7.
Dawson G, Hoinville LJ, Hosie BD, Hunter N (1998) Guidance on the use of PrP genotyping as an aid to the control of clinical scrapie. Vet Rec 142:623–5PubMed
8.
Elsen J-M, Amigues Y, Schelcher F, Ducrocq V, Andreoletti O, Eychenne F, Tien Khang JV, Poivey J-P, Lantier F, Laplance J-L (1999) Genetic susceptibility and transmission factors in scrapie:detailed analysis of an epidemic in a closed flock of Romanov. Arch Virol 144:431–445PubMedCrossRef
9.
Ersdal C, Ulvund MJ, Benestad SL, Tranulis MA (2003) Accumulation of pathogenic prion protein (PrPSc) in nervous and lymphoid tissues of sheep with subclinical scrapie. Vet Pathol 40:164–174PubMedCrossRef
10.
Foster J, McKenzie C, Parnham D, Drummond D, Goldmann W, Stevenson E, Hunter N (2006) Derivation of a scrapie-free sheep flock from the progeny of a flock affected by scrapie. Vet Rec 159:42–45PubMedCrossRef
11.
Fraser H, Dickinson AG (1978) Studies of the lymphoreticular system in the pathogenesis of scrapie: the role of spleen and thymus. J Comp Path 88:563–573PubMedCrossRef
12.
Georgsson G, Sigurdarson S, Brown P (2006) Infectious agent of sheep scrapie may persists in the environment for at least 16 years. J Gen Virol 87:3737–3740PubMedCrossRef
13.
González L, Jeffrey M, Sisó S, Martin S, Bellworthy SJ, Stack MJ, Chaplin MJ, Davis L, Dagleish MP, Reid HW (2005) Diagnosis of preclinical scrapie in samples of rectal mucosa. Vet Rec 156:846–847PubMed
14.
Hadlow WJ, Kennedy RC, Race RE (1982) Natural infection of Suffolk sheep with scrapie virus. J Infect Dis 146:657–664PubMed
15.
Heggebö R, Press CMcL,Gunnes G, González L, Jeffrey M (2002) Distribution and accumulation of PrP in gut-associated and peripheral lymphoid tissue of scrapie-affected Suffolk sheep. J Gen Virol 83:479–489PubMed
16.
Heggebö R, Press CMcL, Gunnes G, Lie KI, Tranulis MA, Ulvund M, Groschup MH, Landsverk T (2000) Distribution 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 81:2327–2337PubMed
17.
Hourrigan J, Klinsporn A, Clark WW, de Camp M (1979) Epidemiology of scrapie in the United States. In: Prusiner SB, Hadlow WJ (eds) Slow transmissible diseases of the nervous system. vol 1. Academic Press, New York, pp 331–356
18.
Huang F-P, Farquhar CF, Mabbott NA, Bruce ME, MacPherson GG (2002) Migrating intestinal dendritic cells transport PrPSc from the gut. J Gen Virol 83:267–271PubMed
19.
Ikegami Y, Ito M, Isomura H, Momotani E, Sasaki K, Muramatsu Y, Ishiguro N, Shinagawa M (1991) Pre-clinical and clinical diagnosis of scrapie by detection of PrP protein in tissues of sheep. Vet Rec 128:271–275PubMedCrossRef
20.
Jeffrey M, McGovern G, Goodsir CM, Brown KL, Bruce ME (2000) Sites of prion protein accumulation in scrapie-infected mouse spleen revealed by immuno-electron microscopy. J Pathol 191:323–332PubMedCrossRef
21.
Johnson CJ, Phillips KE, Schramm PT, McKenzie D, Aiken JM, Pedersen JA (2006) Prions adhere to soil minerals and remain infectious. PloS Pathogens 2:1–7CrossRef
22.
Kimberlin RH, Walker CA (1968) Pathogenesis of scrapie (strain 263K) in hamsters infected intracerebrally, intraperiotoneally or intraocularly. J Gen Virol 67:255–263CrossRef
23.
Lasmézas CI, Cesbron J-Y, Deslys J-P, Demaimay R, Adjou KT, Rioux R, Lemaire C, Locht C, Dormont D (1996) Immune system-dependent and- independent replication of the scrapie agent. J Virol 70:1292–1295PubMed
24.
Ligios C, Sigurdson CJ, Santucciu C, Carcassola G, Manco G, Basagni M, Maestrale C, Cancedda MG, Madau L, Aguzzi A (2005) PrPSc in mammary glands of sheep affected by scrapie and mastitis. Nat Med 11:1137–1138PubMedCrossRef
25.
Ligios C, Cancedda MG, Madau L, Santucciu C, Maestrale C, Agrimi U, Ru G, Di Guardo G (2006) PrPScdeposition in nervous tissues without lymphoid tissue involvement is frequently found in ARQ/ARQ Sarda sheep preclinically affected with natural scrapie. Arch Virol 151:2007–2020PubMedCrossRef
26.
Mabbott NA, Farquhar CF, Brown KL, Bruce ME (1998) Involvement of the immune system in TSE pathogenesis. Immunol Today 5:201–203CrossRef
27.
Mabbott NA, Mackay F, Minns F, Bruce ME (2000) Temporary inactivation of follicular dendritic cells delays neuroinvasion of scrapie. Nat Med 6:719–720PubMedCrossRef
28.
Mabbott NA, MacPherson GG (2006) Prions and their lethal journey to the brain. Nat Rev Microbiol 4:201–211PubMedCrossRef
29.
McBride PA, Eikelenboom P, Kraal G, Fraser H, Bruce ME (1992) PrP protein is associated with follicular dendritic cells of spleens and lymph nodes in uninfected and scrapie-infected mice. J Pathol 168:413–418PubMedCrossRef
30.
McGovern G, Brown KL, Bruce ME, Jeffrey M (2004) Murine scrapie infection causes an abnormal germinal centre reaction in the spleen. J Comp Path 130:181–194PubMedCrossRef
31.
Miller MW, Williams ES, Thompson Hobbs N, Wolfe LL (2004) Environmental sources of prion transmission in mule deer. Emerg Infect Dis 10:1003–1006PubMed
32.
Montrasio F, Frigg R, Glatzel M, Klein MA, Mackay F, Aguzzi A, Weissmann C (2000) Impaired prion replication in spleens of mice lacking functional follicular dendritic cells. Science 288:1257–1259PubMedCrossRef
33.
Muramatsu Y, Onodera A, Horiuchi M, Ishiguro N, Shinagawa M (1993) Detection of PrPSc in sheep at the preclinical stage of scrapie and its siginficance for diagnosis of insidious infection. Arch Virol 134:427–432CrossRef
34.
O’Rourke KI, Baszler TV, Miller JM, Spraker TR, Sadler-Riggleman I, Knowles DP (1998) Monoclonal antibody F89/160.1.5 defines a conserved epitope on the ruminant prion protein. J Clin Microbiol 36:1750–1755PubMed
35.
Palsson PA (1979) Rida (scrapie) in Iceland and its epidemiology. In: Prusiner SB, Hadlow WJ (eds) Slow transmissible diseases of the nervous system. vol 1. Academic Press, New York, pp 357–366
36.
Prusiner SB, Bolton DC, Groth DF, Bowman A, Cochran SP, McKinley MP (1982) Further purification and characterization of scrapie prions. Biochemistry 21:6942–6950PubMedCrossRef
37.
Race R, Jenny A, Sutton D (1998) Scrapie infectivity and proteinase K- resistant prion protein in sheep placenta, brain, spleen, and lymph node: implications for transmission and antemortem diagnosis. J Infect Dis 178:949–953PubMedCrossRef
38.
Roels S, Vanopdenbosch E, Langeveld JPM, Schreuder BEC (1999) Immunohistochemical evaluation of tonsillar tissue for preclinical screening of scrapie based on surveillance in Belgium. Vet Rec 145:524–525PubMedCrossRef
39.
Roels S, Renard C, De Bosschere H, Geeroms R, Van Poucke M, Peelman L, Vanopdenbosch E (2004) Detection of polymorphisms in the prion protein gene in the Belgian sheep population: Some preliminary data. Vet Q 26:3–11PubMed
40.
Schreuder BEC, van Keulen LJM, Vromans MEW, Langeveld JPM, Smits MA (1998) Tonsillar biopsy and PrPSc detection in the preclinical diagnosis of scrapie. Vet Rec 142:564–568PubMedCrossRef
41.
Seeger H, Heikenwalder M, Zeller N, Kranich J, Schwarz P, Gaspert A, Seifert B, Miele G, Aguzzi A (2005) Coincident scrapie infection and nephritis lead to urinary prion excretion. Science 310:324–326PubMedCrossRef
42.
Skarphédinsson S, Jóhannsdóttir R, Gudmundsson P, Sigurdarson S, Georgsson G (1994) PrPSc in Icelandic sheep naturally infected with scrapie. Ann N Y Acad Sci 724:304–309PubMed
43.
Somerville RA, Birkett CR, Farquhar CF, Hunter N, Goldmann W, Dornan J, Grover D, Hennion RM, Percy C, Foster J, Jeffrey M (1997) Immunodetection of PrPSc in spleens of some scrapie-affected sheep but not BSE-infected cows. J GenVirol 78:2389–2396
44.
Thorgeirsdottir S, Sigurdarson S, Thorisson HM, Georgsson G, Palsdottir A (1999) PrP gene polymorphism and natural scrapie in Icelandic sheep. J Gen Virol 80:2527–2534PubMed
45.
Thorgeirsdottir S, Georgsson G, Reynisson E, Sigurdarson S, Palsdottir A (2002) Search for healthy carriers of scrapie: an assessment of subclinical infection of sheep in an Icelandic scrapie flock by three diagnostic methods and correlation with genotypes. Arch Virol 147:709–722PubMedCrossRef
46.
van Keulen LJM, Schreuder BEC, Meloen RH, Mooij- Harkes G, Vromans MEW, Langeveld JPM (1996) Immunohistochemical detection of prion protein in lymphoid tissues of sheep with natural scrapie. J Clin Microbiol 34:1228–1231PubMed
47.
van Keulen LJM, Schreuder BEC, Vromans MEW, Langeweld JPM, Smits MA (1999) Scrapie-associated prion protein in the gastro-intestinal tract of sheep with natural scrapie. J Comp Path 121:55–63PubMedCrossRef
48.
Vascellari M, Nonno R, Mutinelli F, Bigolaro M, Di Bari MA, Melchiotti E, Marcon S, D’Agostino C, Vaccari G, Conte M, De Grossi L, Rosone F, Giordani F, Agrimi U (2007) PrPScin salivary glands of scrapie-affected sheep. J Virol 81:4872–4876PubMedCrossRef
Metadata
Title
High incidence of subclinical infection of lymphoid tissues in scrapie-affected sheep flocks
Authors
Gudmundur Georgsson
Jona Adalheidur Adolfsdottir
Astridur Palsdottir
Einar Jorundsson
Sigurdur Sigurdarson
Stefania Thorgeirsdottir
Publication date
01-04-2008
Publisher
Springer Vienna
Published in
Archives of Virology / Issue 4/2008
Print ISSN: 0304-8608
Electronic ISSN: 1432-8798
DOI
https://doi.org/10.1007/s00705-008-0035-8

Other articles of this Issue 4/2008

Archives of Virology 4/2008 Go to the issue

Original Article

Phosphorylation status of the phosphoprotein P of rinderpest virus modulates transcription and replication of the genome

Annotated Sequence Record

Sequences of the smallest double-stranded RNAs associated with cherry chlorotic rusty spot and Amasya cherry diseases

Annotated Sequence Record

Complete nucleotide sequence of a South African isolate of grapevine leafroll-associated virus 3 reveals a 5′UTR of 737 nucleotides

Brief Report

Genome structure and organization of a member of a novel and distinct species of the genus Caulimovirus associated with dahlia mosaic

Brief Report

Molecular changes in the norovirus polymerase gene and their association with incidence of GII.4 norovirus-associated gastroenteritis outbreaks in Victoria, Australia, 2001–2005

Brief Report

A mosaic of beach bean (Canavalia rosea) caused by an isolate of Cowpea aphid-borne mosaic virus (CABMV) in Brazil
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits