Semen from scrapie-infected rams does not transmit prion infection to transgenic mice

Sarradin, Pierre; Melo, Sandrine; Barc, Céline; Lecomte, C; Andréoletti, Olivier; Lantier, Frédéric; Dacheux, Jean‐Louis; Gatti, Jean‐Luc

doi:10.1530/rep-07-0388

Cited by 12 publications

(19 citation statements)

References 26 publications

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“…These results contrast with those reported by Sarradin et al, (2008). In this study, the semen collected from three classical scrapie infected rams (seminal plasma and spermatozoa) was tested by bioassay in transgenic mice (Tg338) When considered together, these results indicate that infectivity (probably at a limited level) can be present in the semen of a ram infected with classical scrapie.…”

Section: Rubenstein Et Al (2012) Prp Sc Detection and Infectivity Icontrasting

confidence: 79%

Scientific Opinion on the risk of transmission of classical scrapie via in vivo derived embryo transfer in ovine animals

Publication¹

2013

EFS2

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European Food Safety Authority (EFSA), Parma, Italy ABSTRACTThe risk of transmission of classical scrapie via the transfer of in vivo derived embryo in ovines was assessed, taking into account the scientific information made available since the last EFSA opinion on this topic (2010) (see http://www.efsa.europa.eu/en/efsajournal/pub/1429.htm). The potential impact of PrP genotype of the embryo and/or of the ram and donor ewe on this risk was also assessed. The new data made available over the last three years further reinforce the view that classical scrapie could be vertically transmitted in sheep. Since the possibility of such vertical transmission was already considered in the previous opinion, its conclusions and recommendations relating to the risk of classical scrapie transmission via embryo transfer remain valid. In ovines, the susceptibility to classical scrapie infection in sheep is strongly influenced by certain polymorphisms of the PrP gene. Under natural exposure conditions, animals that are heterozygous or homozygous A 136 R 154 R 171 display respectively a low or negligible risk of being infected. The genetic control of the susceptibility to classical scrapie is also likely to impact on the risk of transmitting the disease via embryo transfer. Irrespective of the embryo's genotype, embryos derived from rams and dams carrying at least one ARR allele would significantly decrease this risk (compared to an embryo from parents of unknown genotypes). The use of homozygous ARR embryos would provide the highest level of safety regarding the risk of transmitting classical scrapie through embryo transfer (in vivo derived embryos). The use of heterozygous ARR embryos would ensure a higher level of safety compared to Q 171 /Q 171 embryos. Finally, it was concluded that, providing the OIE recommendations and procedures relating to embryo transfer are adhered to, the risk of transmitting classical scrapie due to the transfer of homozygous or heterozygous ovine ARR embryos can be considered negligible. SUMMARYFollowing a request from the European Commission, the Panel on Biological Hazards (BIOHAZ) was asked to deliver a scientific opinion on the risk of transmission of classical scrapie via in vivo derived embryo transfer in ovine. The Panel was requested to provide an updated scientific opinion on the risk of transmission of classical scrapie via in vivo derived embryo transfer in ovine animals, taking into account any new scientific information made available since its last assessment on this issue in 2010 4 . In addition, the Panel was requested to elaborate on this risk of transmission according to the PrP genotype of the embryo and/or of the ram and donor ewe.The Panel reviewed the scientific literature published since the adoption of the previous Opinion covering this issue in 2010 and concluded that relevant findings available further reinforce the view that classical scrapie in small ruminants could be vertically transmitted. Since the possibility of vertical transmission was already considered in the pr...

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Section: Rubenstein Et Al (2012) Prp Sc Detection and Infectivity Icontrasting

confidence: 79%

Scientific Opinion on the risk of transmission of classical scrapie via in vivo derived embryo transfer in ovine animals

Publication¹

2013

EFS2

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“…Homogenate was spun down at 805 g for 45 s and resulting pellet was discarded. Presence of PrP [27][28][29][30] was confirmed by WB as explained below. Samples were stored at -20 °C.…”

Section: Methodsmentioning

confidence: 87%

“…[25][26][27] A potential route for prion transmission that remains poorly explored involves sexual contact. Although few studies have been done to explore the presence of infectious prions in semen from scrapie affected animals, 28,29 no infectivity (at least to our knowledge) has been reported in testes or any other sexual tissue from male or female animals.…”

Section: Research Papermentioning

confidence: 83%

“…Brain homogenates from males and females having sexual contact with infected animals were tested for WB (A) and PMca (C). The brain of the uninfected animal depicted in the breeding is the one tested for PrP [27][28][29][30] by either WB or PMca. Brain homogenates of pups coming from infected mothers or fathers were also tested by WB (B) and PMca (D).…”

Section: Western Blotting Of Prp 27-30mentioning

confidence: 99%

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Lack of prion transmission by sexual or parental routes in experimentally infected hamsters

Morales

Pritzkow

et al. 2013

Prion

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Prion diseases are a group of neurodegenerative disorders affecting humans as well as captive and wild animals. The mechanisms and routes governing the natural spread of prions are not completely understood and several hypotheses have been proposed. In this study, we analyzed the effect of gender in prion incubation period, as well as the possibility of prion transmission by sexual and parental contact using 263K infected hamsters as a model. Our results show that males have significantly longer incubation periods compared with females when exposed to the same quantity of infectious material. Importantly, no evidence of sexual or parental prion transmission was found, even 500 d after sexual contact or birth, respectively. Western blotting and PMCA were unable to detect sub-clinical levels of PrP(Sc) in experimental subjects, suggesting a complete absence of prion transmission by these routes. Our results show that sexual and parental transmission of prions does not occur in this model. It remains to be studied whether this conclusion is valid also for other prion strains and species.

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“…Embryo transfer and artificial insemination are widely used in animal husbandry and, therefore, assessing presence of prions in embryos and semen could be of interest, although not for diagnostic purposes. Although the first bioassay study failed to transmit scrapie in to transgenic mice by inoculation of scrapie-affected ram semen [341], the possible natural infection of several ewes in a scrapie free-flock that had been bred with likely scrapie-infected rams led Rubenstein and colleagues to use PMCA to detect scrapie prions in semen of experimentally infected rams, demonstrating low levels of seeding activity [342]. The same methodology applied to semen samples of CWD-infected deer also confirmed the presence of prions in this body fluid, albeit with low sensitivity, probably due to the low titers [343].…”

Section: Detection Of Prp Sc In Other Tissues and Body Fluidsmentioning

confidence: 99%

Detection of Pathognomonic Biomarker PrPSc and the Contribution of Cell Free-Amplification Techniques to the Diagnosis of Prion Diseases

et al. 2020

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Transmissible spongiform encephalopathies or prion diseases are rapidly progressive neurodegenerative diseases, the clinical manifestation of which can resemble other promptly evolving neurological maladies. Therefore, the unequivocal ante-mortem diagnosis is highly challenging and was only possible by histopathological and immunohistochemical analysis of the brain at necropsy. Although surrogate biomarkers of neurological damage have become invaluable to complement clinical data and provide more accurate diagnostics at early stages, other neurodegenerative diseases show similar alterations hindering the differential diagnosis. To solve that, the detection of the pathognomonic biomarker of disease, PrP Sc , the aberrantly folded isoform of the prion protein, could be used. However, the amounts in easily accessible tissues or body fluids at pre-clinical or early clinical stages are extremely low for the standard detection methods. The solution comes from the recent development of in vitro prion propagation techniques, such as Protein Misfolding Cyclic Amplification (PMCA) and Real Time-Quaking Induced Conversion (RT-QuIC), which have been already applied to detect minute amounts of PrP Sc in different matrixes and make early diagnosis of prion diseases feasible in a near future. Herein, the most relevant tissues and body fluids in which PrP Sc has been detected in animals and humans are being reviewed, especially those in which cell-free prion propagation systems have been used with diagnostic purposes.

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Semen from scrapie-infected rams does not transmit prion infection to transgenic mice

Cited by 12 publications

References 26 publications

Scientific Opinion on the risk of transmission of classical scrapie via in vivo derived embryo transfer in ovine animals

Scientific Opinion on the risk of transmission of classical scrapie via in vivo derived embryo transfer in ovine animals

Lack of prion transmission by sexual or parental routes in experimentally infected hamsters

Detection of Pathognomonic Biomarker PrPSc and the Contribution of Cell Free-Amplification Techniques to the Diagnosis of Prion Diseases

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