Pregnancy status and fetal prion genetics determine PrP
            <sup>Sc</sup>
            accumulation in placentomes of scrapie-infected sheep

Tuo, Wenbin; O’Rourke, Katherine I.; Zhuang, Dongyue; Cheevers, William P.; Spraker, Terry R.; Knowles, Donald P.

doi:10.1073/pnas.072071199

Cited by 74 publications

(73 citation statements)

References 30 publications

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“…Infection of placental membranes is reportedly restricted to susceptible fetal genotypes. 36 In this study, transmission followed ewe-to-lamb lines in most scrapie-affected sheep, and there was abundant PrP sc deposition within and around placental trophoblast cells. PrP sc was not evident in 2 genetically susceptible fetuses, supporting other studies arguing against direct intrauterine transmission of scrapie or infectivity of the fetus proper.…”

Section: Discussionmentioning

confidence: 97%

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Biology of PrP^sc Accumulation in Two Natural Scrapie-Infected Sheep Flocks

Caplazi

O’Rourke²,

Wolf

et al. 2004

J VET Diagn Invest

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Abstract. Sheep scrapie is a prion disease that requires interaction of exogenous prions with host prion protein (PrP) supporting prion formation. Disease is associated with deposition of a host-generated conformational variant of PrP, PrP sc , in a variety of tissues, including brain, resulting in fatal spongiform encephalopathy. Efficiency of PrP sc formation is determined by polymorphisms in the PrP-coding sequence. This article adds to previous data of natural sheep scrapie, concentrating on the effect of host genotype and age on PrP sc accumulation patterns during preclinical and clinical disease. Two entire scrapie-infected, predominantly Suffolk-cross, sheep flocks euthanized for regulatory purposes were genotyped and analyzed for PrP sc deposition in various tissues using single-and dual-label immunohistochemistry. Scrapie, as defined by PrP sc deposition, occurred in 13/80 sheep. Preclinical disease was evident in nearly 70% of infected sheep, ranging in age from 14 months to 7 years. PrP sc accumulated systemically in the nervous tissue, various lymphoid tissues, both alimentary tract related and non-alimentary tract related, and the placenta. Clinical neurological illness was always associated with spongiform encephalopathy and PrP sc deposition in the brain. Only 6 of 9 sheep with preclinical scrapie had PrP sc deposition in the brain but widespread PrP sc deposition in peripheral lymphoid tissue, supporting previous data showing peripheral PrP sc accumulation preceding deposition in the brain. PrP sc colocalized with a marker for follicular dendritic cells throughout the lymphoid system. PrP sc also accumulated in the peripheral nervous system, particularly the nervous supply of the gastrointestinal tract. Abundant PrP sc was evident in trophoblast cells of placentomes but not in the endometrium, myometrium, or associated nervous plexus. PrP sc deposits were not observed in the mammary parenchyma or bone marrow. Scrapie susceptibility was defined genetically by PrP codon 171: PrP sc deposition was restricted to PrP genotype AA 136 RR 154 QQ 171 in 12/13 cases or AV 136 RR 154 QQ 171 in 1/13 cases. The earliest accumulation was observed in the single VRQ/ARQ heterozygous animal, consistent with the reported high scrapie susceptibility and brief incubation period observed in breeds with predominance of the V 136 R 154 Q 171 allele. Disease occurred within, as well as independent of, motherdaughter lines, suggesting both maternal and nonmaternal transmission in the flocks.

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Section: Discussionmentioning

confidence: 97%

“…Two fetuses from PrP scpositive ewes with clinical scrapie were available for examination. Both ewes had PrP sc deposition in the placenta, proving the scrapie-susceptible genotype of the fetus, 36 but neither fetus had PrP sc deposition in fetal spleen or intestine ( Table 2).…”

Section: F Subiliac Lymph Node Germinal Center (Clinical) Prp Sc (Bmentioning

confidence: 99%

Biology of PrP^sc Accumulation in Two Natural Scrapie-Infected Sheep Flocks

Caplazi

O’Rourke²,

Wolf

et al. 2004

J VET Diagn Invest

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“…26,22,34 N-terminally truncated and glycosylated PrP C that migrates at ϳ23 to 37 kDa, has been observed in cotyledonary chorioallantois, allantoic fluid, endometrium, myometrium, oviduct, and ovary of pregnant and nonpregnant uninfected ewes. 22 In addition, PrP C in low or undetectable amounts was observed in intercotyledonary chorioallantois, amnion, and amniotic fluid.…”

Section: Discussionmentioning

confidence: 99%

“…22 By immunohistochemistry, PrP Sc staining was observed mainly in the uterine endometrial epithelium, trophoblast cells, and multinucleate cells in zone A of the maternal endometrial crypts of scrapie-infected ewes. 34 Interestingly, the rPrP Sc bands present in sheep placenta had lower molecular mass than did corresponding bands from the brain. 26 It has been proposed that the differences in the size and glycosylation patterns of the PK-resistant PrP in the placenta and brain represent unique PrP Sc processing in different tissues.…”

Section: Discussionmentioning

confidence: 99%

“…26,35 Although our current study did not detect abnormal PrP species in the uterus and gestational tissues, including the placenta and amniotic fluid from this CJD case, it must be emphasized that only portions of the uterine and placental tissues were examined. Given localization of PrP Sc only in certain areas of the uterus and placenta of the infected ewes, 22,34 additional studies on more areas of these organs from gravid women with CJD are needed. Moreover, whether these tissues are infectious remains to be further determined by bioassay.…”

Section: Discussionmentioning

confidence: 99%

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Failure to Detect the Presence of Prions in the Uterine and Gestational Tissues from a Gravida with Creutzfeldt-Jakob Disease

Xiao

Miravalle

Yuan

et al. 2009

The American Journal of Pathology

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The vertical transmission of a prion disease from infected mothers to their offspring is believed to be one of the routes for the natural spread of animal prion diseases. Supporting this notion is the observation that prion infectivity occurs in the placenta of infected ewes. Furthermore, the prion protein (PrP), both in its cellular form (PrP C ) and its pathological isoform (PrP Sc ), has been observed at the fetal-maternal interface of scrapie-infected sheep. However, whether these features of prion infectivity also hold true for human prion diseases is currently unknown. To begin to address such an important question, we examined PrP in the uterus as well as gestational tissues, including the placenta and amniotic fluid, in a pregnant woman with sporadic Creutzfeldt-Jakob disease (CJD). Although the proteinase K (PK)-resistant prion protein, PrP27-30, was present in the brain tissues of the mother, the PrP detected in the uterus, placenta, and amniotic fluid was sensitive to PK digestion. Unlike PrP C in the brain and adjacent cerebrospinal fluid, the predominant PrP species in the reproductive and gestational tissues were N-terminally truncated, similar to urine PrP. Our study did not detect abnormal PrP in the reproductive and gestational tissues in this case of CJD. Nevertheless, examination by a highly sensitive bioassay is ongoing to ascertain possible prion infectivity from CJD in the amniotic fluid.

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Do Animal Transmissible Spongiform Encephalopathies Pose a Risk for Human Health?

Schmerr¹

2004

Preharvest and Postharvest Food Safety

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Pregnancy status and fetal prion genetics determine PrP ^Sc accumulation in placentomes of scrapie-infected sheep

Abstract: Ovine scrapie is a fatal neurodegenerative disorder that may be transmitted through exposure to infected uterine and placental tissues. Susceptibility to scrapie is primarily controlled by polymorphisms in the prion protein (

Cited by 74 publications

References 30 publications

Biology of PrP^sc Accumulation in Two Natural Scrapie-Infected Sheep Flocks

Biology of PrP^sc Accumulation in Two Natural Scrapie-Infected Sheep Flocks

Failure to Detect the Presence of Prions in the Uterine and Gestational Tissues from a Gravida with Creutzfeldt-Jakob Disease

Do Animal Transmissible Spongiform Encephalopathies Pose a Risk for Human Health?

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Pregnancy status and fetal prion genetics determine PrP Sc accumulation in placentomes of scrapie-infected sheep

Abstract: Ovine scrapie is a fatal neurodegenerative disorder that may be transmitted through exposure to infected uterine and placental tissues. Susceptibility to scrapie is primarily controlled by polymorphisms in the prion protein (

Cited by 74 publications

References 30 publications

Biology of PrPsc Accumulation in Two Natural Scrapie-Infected Sheep Flocks

Biology of PrPsc Accumulation in Two Natural Scrapie-Infected Sheep Flocks

Failure to Detect the Presence of Prions in the Uterine and Gestational Tissues from a Gravida with Creutzfeldt-Jakob Disease

Do Animal Transmissible Spongiform Encephalopathies Pose a Risk for Human Health?

Contact Info

Product

Resources

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Pregnancy status and fetal prion genetics determine PrP ^Sc accumulation in placentomes of scrapie-infected sheep

Biology of PrP^sc Accumulation in Two Natural Scrapie-Infected Sheep Flocks

Biology of PrP^sc Accumulation in Two Natural Scrapie-Infected Sheep Flocks