Foodborne-Transmitted Prions From the Brain of Cows With Bovine Spongiform Encephalopathy Ascend in Afferent Neurons to the Simian Central Nervous System and Spread to Tonsils and Spleen at a Late Stage of the Incubation Period

Holznagel, Edgar; Yutzy, Barbara; Kruip, Carina; Bierke, P; Schulz‐Schaeffer, Walter; Löwer, Johannes

doi:10.1093/infdis/jiv232

Cited by 10 publications

(14 citation statements)

References 29 publications

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“…Foodborne BSE prions enter the CNS of macaques (Macaca fascicularis, cynomolgus monkey) via afferent neurons, spreading centrifugally to lymphoid tissue at an advanced stage of the incubation period. In asymptomatic animals PrP was detected in 50 % and 12 %, of gut-and tonsil-derived samples, respectively (Holznagel et al 2015). PrP was also detected in non-CNS tissues (spleen, lymph node, and marrow) in at least 50 % of these infected macaques (Holznagel et al, 2010).…”

Section: In Vivo Methods Using Primates For the Study Of The Moleculamentioning

confidence: 99%

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Scientific Opinion on a request for a review of a scientific publication concerning the zoonotic potential of ovine scrapie prions

2015

EFSA Journal

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The factors that modulate the transmissibility of Transmissible Spongiform Encephalopathies (TSE) and the approaches for the study of their zoonotic potential are reviewed. The paper 'Evidence for zoonotic potential of ovine scrapie prions' by Cassard et al. (2014) is scientifically appraised, focussing on the experimental design, the results and the conclusions. The paper provides evidence in a laboratory experiment that some Classical scrapie isolates can propagate in humanised transgenic mice and produce prions that on second passage are similar to those causing one form of sporadic Creutzfeldt-Jakob disease (sCJD). It is concluded that the results from the study raise the possibility that scrapie prions have the potential to be zoonotic, but do not provide evidence that transmission can or does take place under field conditions. The conclusions of the 2011 ECDC-EFSA 'Joint Scientific Opinion on any possible epidemiological or molecular association between TSEs in animals and humans' are reviewed in the light of the new scientific evidence available since its publication. This supports and strengthens the conclusions of that opinion with regard to the potential for some animal TSE to be zoonotic, but does not provide evidence of a causal link between Classical or Atypical scrapie and human TSE. Current evidence does not establish this link, and no consistent risk factors have been identified for sCJD. The possibility of scrapie-related public health risks from the consumption of ovine products cannot be assessed. Recommendations are formulated on further studies and data that are needed to investigate the zoonotic potential of animal TSE and to estimate the amount of infectivity from TSE-infected products sourced from small ruminants and entering the food chain in the European Union. © European Food Safety Authority, 2015Keywords: Atypical scrapie, Classical scrapie, Creutzfeldt-Jakob disease, transmissible spongiform encephalopathy, zoonosis Amendment: An amendment has been made to the following sentence on p. 31: 'In this regard the emergence of sCJD is not so surprising, and has been described after inoculation of tgHu mice with cattle BSE and human vCJD (Asante et al., 2002;Beringue et al., 2008b)'. This was carried out to clarify that one of the references reported emergence of sporadic CJD after experimental inoculation of humanised transgenic mice with vCJD, which was not correctly stated in the published opinion. An amendment has been made on p. 28, to add the word 'OR' between two search terms within the literature search string reported. Reproduction is authorised provided the source is acknowledged. Requestor: European CommissionThe EFSA Journal is a publication of the European Food Safety Authority, an agency of the European Union. SummaryFollowing a request from the European Commission (EC), the EFSA Panel on Biological Hazards (BIOHAZ Panel) was asked to deliver a scientific opinion on the review of a scientific publication concerning the zoonotic potential of ovine scrapie prions.T...

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Section: In Vivo Methods Using Primates For the Study Of The Moleculamentioning

confidence: 99%

“…In asymptomatic animals PrP was detected in 50 % and 12 %, of gut-and tonsil-derived samples, respectively (Holznagel et al 2015). PrP was also detected in non-CNS tissues (spleen, lymph node, and marrow) in at least 50 % of these infected macaques (Holznagel et al, 2010).…”

Section: Overexpressing Transgenic Micementioning

confidence: 99%

Scientific Opinion on a request for a review of a scientific publication concerning the zoonotic potential of ovine scrapie prions

2015

EFSA Journal

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“…We demonstrated this paradigm earlier in severely immunodeficient (SCID) mice infected with mouse-adapted scrapie 22) . Moreover, spread from the gut to the CNS via autonomic nerve fibers has been shown in experimental scrapie and BSE [23][24][25] . Fig.…”

Section: Fig 2 Pathological Prp Deposits In Peyer's Patches Of Bse mentioning

confidence: 99%

Modeling Variant Creutzfeldt-Jakob Disease and Its Pathogenesis in Non-human Primates

Lasmézas

2017

Food Safety

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In the early 90s', Europe was shaken by the fear that the prions from "mad cow disease" (bovine spongiform encephalopathy) would transmit the disease to humans via beef products. In 1996, the first variant Creutzfeldt-Jakob (vCJD) patients were described, and the same year our Bovine Spongiform Encephalopathy (BSE) transmission studies to cynomolgus macaques demonstrated that the BSE prion was highly infectious for primates, inducing brain lesions identical to those observed in vCJD patients. These studies provided the first experimental evidence that vCJD was BSE in humans. Subsequent studies established the BSE/vCJD-infected cynomolgus macaque as a robust model to study the pathogenesis of vCJD. We showed rapid adaptation of BSE prions to primates upon subsequent passage, and their distribution in peripheral tissues and blood. Some key studies are summarized in the present paper.

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“…In contrast, most macaques showed invasion of the CNS primarily at the level of the lumbar spinal cord, which was obviously mediated by anterograde spread along visceral afferents. PrP TSE accumulation in dorsal root ganglia preceded PrP TSE deposition in the corresponding dorsal horn, with initial accumulations in the substantia gelatinosa [ 56 ].…”

Section: The Established Neural Gut–brain Axis In Peroral Prion Infectionsmentioning

confidence: 99%

The Neural Gut–Brain Axis of Pathological Protein Aggregation in Parkinson’s Disease and Its Counterpart in Peroral Prion Infections

Beekes

2021

Viruses

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A neuropathological hallmark of Parkinson’s disease (PD) is the cerebral deposition of abnormally aggregated α-synuclein (αSyn). PD-associated αSyn (αSynPD) aggregates are assumed to act, in a prion-like manner, as proteinaceous nuclei (“seeds”) capable of self-templated propagation. Braak and colleagues put forward the idea of a neural gut-brain axis mediating the centripetal spread of αSynPD pathology from the enteric nervous system (ENS) to the brain in PD. This has sparked great interest and initiated passionate discussions both in support of and opposing the suggested hypothesis. A precedent for the spread of protein seeds or seeding from the gastro-intestinal (GI) tract to the central nervous system (CNS) had been previously revealed for pathological prion protein in peroral prion infections. This article scrutinizes the similarities and dissimilarities between the pathophysiological spread of disease-associated protein aggregation along the neural gut–brain axis in peroral prion infections and PD. On this basis, evidence supporting the proposed neural gut–brain axis in PD is concluded to be not as robust as that established for peroral prion infections. New tools for the ultrasensitive detection of αSynPD-associated seeding activity in archived or fresh human tissue samples such as real-time quaking induced conversion (RT-QuIC) or protein misfolding cyclic amplification (PMCA) assays can possibly help to address this deficit in the future.

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Foodborne-Transmitted Prions From the Brain of Cows With Bovine Spongiform Encephalopathy Ascend in Afferent Neurons to the Simian Central Nervous System and Spread to Tonsils and Spleen at a Late Stage of the Incubation Period

Cited by 10 publications

References 29 publications

Scientific Opinion on a request for a review of a scientific publication concerning the zoonotic potential of ovine scrapie prions

Scientific Opinion on a request for a review of a scientific publication concerning the zoonotic potential of ovine scrapie prions

Modeling Variant Creutzfeldt-Jakob Disease and Its Pathogenesis in Non-human Primates

The Neural Gut–Brain Axis of Pathological Protein Aggregation in Parkinson’s Disease and Its Counterpart in Peroral Prion Infections

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