Placentae from scrapie-affected ewes are an important source of contamination. This study confirmed that scrapie-incubating ewes bearing susceptible genotypes could produce both abnormal prion protein (PrPSc)-positive and -negative placentae, depending only on the PRP genotype of the fetus. The results also provided evidence indicating that scrapie-incubating ARR/VRQ ewes may be unable to accumulate prions in the placenta, whatever the genotype of their progeny. Multinucleated trophoblast cells appeared to play a key role in placental PrPSc accumulation. PrPSc accumulation began in syncytiotrophoblasts before disseminating to uninucleated trophoblasts. As these result from trophoblast/uterine epithelial cell fusion, syncytiotrophoblast cells expressed maternal and fetal PrPC, whilst uninucleated trophoblast cells only expressed fetal PrPC. In ARR/VRQ scrapie-infected ewes, expression of the ARR allele by syncytiotrophoblasts appeared to prevent initiation of PrPSc placental deposition. The absence of prions in affected ARR/VRQ sheep placentae reinforces strongly the interest in ARR selection for scrapie control.
AlversonJ.,
O'RourkeK. I.,
BaszlerT. V.2006; PrPSc accumulation in fetal cotyledons of scrapie-resistant lambs is influenced by fetus location in the uterus. J Gen Virol 87:1035–1041[CrossRef]
AndréolettiO.,
LacrouxC.,
ChabertA.,
MonnereauL.,
TabouretG.,
LantierF.,
BerthonP.,
EychenneF.,
Lafond-BenestadS.other authors2002b; 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 83:2607–2616
ClouscardC.,
BeaudryP.,
ElsenJ. M.,
MilanD.,
DussaucyM.,
BounneauC.,
SchelcherF.,
ChatelainJ.,
LaunayJ. M.,
LaplancheJ.-L.1995; Different allelic effects of the codons 136 and 171 of the prion protein gene in sheep with natural scrapie. J Gen Virol 76:2097–2101[CrossRef]
ElsenJ.-M.,
AmiguesY.,
SchelcherF.,
DucrocqV.,
AndréolettiO.,
EychenneF.,
KhangJ. V.,
PoiveyJ.-P.,
LantierF.,
LaplancheJ.-L.1999; Genetic susceptibility and transmission factors in scrapie: detailed analysis of an epidemic in a closed flock of Romanov. Arch Virol 144:431–445[CrossRef]
HunterN.,
FosterJ. D.,
GoldmannW.,
StearM. J.,
HopeJ.,
BostockC.1996; Natural scrapie in a closed flock of Cheviot sheep occurs only in specific PrP genotypes. Arch Virol 141:809–824[CrossRef]
HunterN.,
GoldmannW.,
FosterJ. D.,
CairnsD.,
SmithG.1997; Natural scrapie and PrP genotype: case-control studies in British sheep. Vet Rec 141:137–140[CrossRef]
RaceR.,
JennyA.,
SuttonD.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 178:949–953[CrossRef]
RaceR.,
RainesA.,
RaymondG. J.,
CaugheyB.,
ChesebroB.2001; Long-term subclinical carrier state precedes scrapie replication and adaptation in a resistant species: analogies to bovine spongiform encephalopathy and variant Creutzfeldt–Jakob disease in humans. J Virol 75:10106–10112[CrossRef]
SchreuderB. E.,
van KeulenL. J.,
VromansM. E.,
LangeveldJ. P.,
SmitsM. A.1998; Tonsillar biopsy and PrPSc detection in the preclinical diagnosis of scrapie. Vet Rec 142:564–568[CrossRef]
Schulz-SchaefferW. J.,
TschokeS.,
KranefussN.,
DroseW.,
Hause-ReitnerD.,
GieseA.,
GroschupM. H.,
KretzschmarH. A.2000; The paraffin-embedded tissue blot detects PrPSc early in the incubation time in prion diseases. Am J Pathol 156:51–56[CrossRef]
ThomzigA.,
Schulz-SchaefferW.,
KratzelC.,
MaiJ.,
BeekesM.2004; Preclinical deposition of pathological prion protein PrPSc in muscles of hamsters orally exposed to scrapie. J Clin Invest 113:1465–1472[CrossRef]
TuoW.,
O'RourkeK. I.,
ZhuangD.,
CheeversW. P.,
SprakerT. R.,
KnowlesD. P.2002; Pregnancy status and fetal prion genetics determine PrPSc accumulation in placentomes of scrapie-infected sheep. Proc Natl Acad Sci U S A 99:6310–6315[CrossRef]
van KeulenL. J.,
SchreuderB. E.,
MeloenR. H.,
Mooij-HarkesG.,
VromansM. E.,
LangeveldJ. P.1996a; Immunohistochemical detection of prion protein in lymphoid tissues of sheep with natural scrapie. J Clin Microbiol 34:1228–1231
van KeulenL. J.,
SchreuderB. E.,
MeloenR. H.,
Mooij-HarkesG.,
VromansM. E.,
LangeveldJ. P.1996b; Immunohistochemical detection of prion protein in lymphoid tissues of sheep with natural scrapie. J Clin Microbiol 34:1228–1231
van PouckeM.,
VandesompeleJ.,
MattheeuwsM.,
van ZeverenA.,
PeelmanL. J.2005; A dual fluorescent multiprobe assay for prion protein genotyping in sheep. BMC Infect Dis 5:13[CrossRef]