Archival search for historical atypical scrapie in sheep reveals evidence for mixed infections

Chong, Angela; Kennedy, Iain M.; Goldmann, Wilfred; Green, Andrew; González, Lorenzo; Jeffrey, Martin; Hunter, Nora

doi:10.1099/jgv.0.000234

Cited by 16 publications

(24 citation statements)

References 44 publications

(27 reference statements)

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“…The light microscopic patterns of vacuolation (Figure S3) and PrP d accumulation ( Figure S4) seen in atypical scrapie-infected Tg338 mice were consistent with those previously described [18,27,35]. Of particular note was the dense punctate PrP d accumulation in the dorsal thalamus and the laminar punctuate PrP d accumulation in the mid and deep cerebrocortical layers ( Figure S4) with sparing of cerebellum and hindbrain [18].…”

Section: Atypical Scrapie In Tg338 Micesupporting

confidence: 86%

“…As expected, CH1641-infected Tg338 mice showed patterns of vacuolation ( Figure S3) and PrP d distribution distinct from atypical scrapie-infected Tg338 mice [27]. Electron microscopic examination of CH1641-infected mice confirmed the presence of extracellular amyloid, intra-lysosomal PrP d (in neurons and glia) and membrane lesions typical of classical scrapie.…”

Section: Tg338 Infected With Ch1641 Classical Scrapiesupporting

confidence: 73%

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Altered trafficking of abnormal prion protein in atypical scrapie: prion protein accumulation in oligodendroglial inner mesaxons

Jeffrey

González

Simmons

et al. 2016

Neuropathology Appl Neurobio

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Section: Atypical Scrapie In Tg338 Micesupporting

confidence: 86%

Section: Tg338 Infected With Ch1641 Classical Scrapiesupporting

confidence: 73%

Altered trafficking of abnormal prion protein in atypical scrapie: prion protein accumulation in oligodendroglial inner mesaxons

Jeffrey

González

Simmons

et al. 2016

Neuropathology Appl Neurobio

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“…The coexistence of multiple prion strains in the same host is a well-known phenomenon in scrapie-affected sheep (22), in mink with transmissible mink encephalopathy (23), and in sCJD patients carrying both type 1 and type 2 PrP TSE in the brain. However, the isolation of a given prion strain occurs only after several passages in the same host species, which depends on the preferential propagation of one or another strain dictated by the host tropism (24).…”

Section: Discussionmentioning

confidence: 99%

Prion Strain Characterization of a Novel Subtype of Creutzfeldt-Jakob Disease

Galeno

Bari

Nonno

et al. 2017

J Virol

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In 2007, we reported a patient with an atypical form of CreutzfeldtJakob disease (CJD) heterozygous for methionine-valine (MV) at codon 129 who showed a novel pathological prion protein (PrP TSE ) conformation with an atypical glycoform (AG) profile and intraneuronal PrP deposition. In the present study, we further characterize the conformational properties of this pathological prion protein (PrP TSE MV AG ), showing that PrP TSE MV AG is composed of multiple conformers with biochemical properties distinct from those of PrP TSE type 1 and type 2 of MV sporadic CJD (sCJD). Experimental transmission of CJD-MV AG to bank voles and genetargeted transgenic mice carrying the human prion protein gene (TgHu mice) showed unique transmission rates, survival times, neuropathological changes, PrP TSE deposition patterns, and PrP TSE glycotypes that are distinct from those of sCJD-MV1 and sCJD-MV2. These biochemical and experimental data suggest the presence of a novel prion strain in CJD-MV AG .IMPORTANCE Sporadic Creutzfeldt-Jakob disease is caused by the misfolding of the cellular prion protein, which assumes two different major conformations (type 1 and type 2) and, together with the methionine/valine polymorphic codon 129 of the prion protein gene, contribute to the occurrence of distinct clinical-pathological phenotypes. Inoculation in laboratory rodents of brain tissues from the six possible combinations of pathological prion protein types with codon 129 genotypes results in the identification of 3 or 4 strains of prions. We report on the identification of a novel strain of Creutzfeldt-Jakob disease isolated from a patient who carried an abnormally glycosylated pathological prion protein. This novel strain has unique biochemical characteristics, does not transmit to humanized transgenic mice, and shows exclusive transmission properties in bank voles. The identification of a novel human prion strain improves our understanding of the pathogenesis of the disease and of possible mechanisms of prion transmission.

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“…Molecular markers are shown on the left side (kDa).; lane 7) with mAb P4 revealed the same multiple banding pattern as the atypical scrapie positive control (Fig. 1; lanes 1 and 2), exhibiting a characteristic low-molecular fragment at ~7 kDa [6, 14, 26] which is clearly not present in the classical scrapie positive control (Fig. 1; lane 10).…”

mentioning

confidence: 79%

“…The PRNP genotype of the present case was AF 141 RQ/AF 141 RQ, which is known to be highly susceptible to atypical scrapie compared to the wild-type AL 141 RQ [6, 10, 12, 21]. The PRNP genotype rate from 975 sheep sampled between April 2003 and May 2016 was as follows: ARQ/ARQ, 46.5%; ARQ/ARR, 30.9%; and ARR/ARR, 10.1% (Table 2…”

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confidence: 99%

Identification of the first case of atypical scrapie in Japan

Imamura

Miyazawa

Iwamaru

et al. 2016

The Journal of Veterinary Medical Science

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A Corriedale ewe was confirmed as the first atypical scrapie case during an active surveillance program for transmissible spongiform encephalopathies in small ruminants in Japan. The animal was homozygous for the AF141RQ haplotype of PRNP. The animal showed clinical neurological signs possibly due to listeriosis before culling. Western blot analysis showed an unusual multiple banded pattern with a low-molecular fragment at ~7 kDa. Histopathology revealed suppurative meningoencephalitis caused by listeriosis in the brainstem. Fine granular to globular immunostaining of disease-associated prion proteins was mainly detected in the neuropil of the spinal tract of the trigeminal nerve and in the white matter of the spinocerebellar tract. Based on these results, this case was conclusively diagnosed as atypical scrapie with encephalitic listeriosis.

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Archival search for historical atypical scrapie in sheep reveals evidence for mixed infections

Cited by 16 publications

References 44 publications

Altered trafficking of abnormal prion protein in atypical scrapie: prion protein accumulation in oligodendroglial inner mesaxons

Altered trafficking of abnormal prion protein in atypical scrapie: prion protein accumulation in oligodendroglial inner mesaxons

Prion Strain Characterization of a Novel Subtype of Creutzfeldt-Jakob Disease

Identification of the first case of atypical scrapie in Japan

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