Cultured Peripheral Neuroglial Cells Are Highly Permissive to Sheep Prion Infection

Archer, Fabienne; Bachelin, Corinne; Andréoletti, Olivier; Besnard, Nathalie; Perrot, Grégory; Langevin, Christelle; Dur, Annick Le; Vilette, Didier; Evercooren, Anne Baron-Van; Vilotte, Jean–Luc; Laude, Hubert

doi:10.1128/jvi.78.1.482-490.2004

Cited by 80 publications

(103 citation statements)

References 63 publications

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“…The material used for infection was prepared from the brain of terminally ill tg338 mice inoculated with the 127S scrapie strain (21) or from MovS2 cells, an immortalized Schwann cell line originally derived from tg338 mice and infected with the 127S strain [ScMov cells (14)]. Ten percent brain homogenates were prepared in PBS and stored at Ϫ20°C until use.…”

Section: Methodsmentioning

confidence: 99%

“…We next examined the permissiveness of CGN 338 cultures to infection by sheep prion. As a source of infectious agent, we used a strain of natural sheep scrapie that can propagate in permissive cell lines expressing ovine PrP (14,31) and in tg338 mice, leading to death within 60 days (21). Unlike established cell systems involving actively dividing cells, neuron cultures do not allow washing out of the inoculum or subpassage cells.…”

Section: Primary Cultures Of Mouse Cerebellar Cells Expressing Sheep mentioning

confidence: 99%

“…Immortalized neuronal and neuroglial cell lines persistently infected by prions generally show no overt signs of cytotoxicity, although producing readily detectable amounts of PrP Sc and infectivity (12)(13)(14)(15). Various phenotypical alterations have been reported (16,17), yet it remains uncertain whether similar dysfunctions may affect TSE-injured postmitotic neurons.…”

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confidence: 99%

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Prions can infect primary cultured neurons and astrocytes and promote neuronal cell death

Cronier

Laude

Peyrin

2004

Proc. Natl. Acad. Sci. U.S.A.

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138

150

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Transmissible spongiform encephalopathies arise as a consequence of infection of the central nervous system by prions, where neurons and glial cells are regarded as primary targets. Neuronal loss and gliosis, associated with the accumulation of misfolded prion protein (PrP), are hallmarks of prion diseases; yet the mechanisms underlying such disorders remain unclear. Here we introduced a cell system based on primary cerebellar cultures established from transgenic mice expressing ovine PrP and then exposed to sheep scrapie agent. Upon exposure to low doses of infectious agent, such cultures, unlike cultures originating from PrP null mice, were found to accumulate de novo abnormal PrP and infectivity, as assessed by mouse bioassay. Importantly, using astrocyte and neuron͞astrocyte cocultures, both cell types were found capable of sustaining efficient prion propagation independently, leading to the production of proteinase K-resistant PrP of the same electrophoretic profile as in diseased brain. Moreover, contrasting with data obtained in chronically infected cell lines, late-occurring apoptosis was consistently demonstrated in the infected neuronal cultures. Our results provide evidence that primary cultured neural cells, including postmitotic neurons, are permissive to prion replication, thus establishing an approach to study the mechanisms involved in prion-triggered neurodegeneration at a cellular level.T ransmissible spongiform encephalopathies (TSE), which include Creutzfeldt-Jakob disease in humans, bovine spongiform encephalopathy in cattle, and scrapie in sheep, are fatal neurodegenerative disorders caused by prions, a class of unconventional agents that targets the CNS in mammals. A hallmark of prion diseases is the accumulation of abnormal prion protein (PrP Sc ), a misfolded form of the cellular PrP (PrP c ). Transmissibility is believed to stem from the ability of the prion isoform to promote the conformational transition from PrP c to PrP Sc . Biologically distinct prion strains can propagate in a same host, presumably through the perpetuation of different specific PrP Sc conformers (1-3).Although it seems clear that neuronal dysfunction must lie at the root of the clinical disorders observed in these diseases, it is still obscure what triggers neurodegeneration and what role nonneuronal cells may play in this process. There is ample evidence to support a primary role of the neurons in prion propagation and neuropathogenesis into the CNS. Intra-or perineuronal PrP Sc deposition, spongiform vacuolation involving cell soma and processes, and neuronal loss are typical histopathological changes observed in TSE-affected brain tissues (4, 5). Transgenic mice with PrP expression specifically targeted to neurons have been obtained that turned out to be fully susceptible to prion disease (6). More recently, it was shown that an acute neuron-targeted depletion of PrP in the brain of mice with ongoing infection is able to prevent neuronal loss and progression to disease and even to reverse early spongiform chang...

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Section: Methodsmentioning

confidence: 99%

Section: Primary Cultures Of Mouse Cerebellar Cells Expressing Sheep mentioning

confidence: 99%

mentioning

confidence: 99%

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Prions can infect primary cultured neurons and astrocytes and promote neuronal cell death

Cronier

Laude

Peyrin

2004

Proc. Natl. Acad. Sci. U.S.A.

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138

150

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“…The resulting cultures, known as Rov cells, can be readily infected with and replicate to high titres some sheep scrapie isolates [146]. Neuroglial cell lines with Schwann-like features [3] and primary cultures of neurons and astrocytes [34], both of which were derived from transgenic mice expressing the VRQ allele of ovine PrP C , were later shown to be permissive to sheep scrapie as well. Finally, prion propagation and PrP res accumulation were also demonstrated in an astrocyte-like, sheep-derived cell line [145] inoculated with the same set of ovine prion agents ( [75] and our unpublished results).…”

Section: Cell Models Propagating Naturally-occurring Prion Isolatesmentioning

confidence: 99%

“…In the absence of nucleic acids, strain biological properties are proposed to be encoded by the abnormal PrP [150]. The PrP res banding patterns of strains generated in cultured cells are often, but not always [34], different from those generated in the brain [3,4,26,90,95,146] but return to the original brain pattern upon animal inoculation [3,4]. This confirmed that the cellular context in which multiplication occurs has a determinant effect on the glycoforms and on the size of the abnormal PrP species and that modifications of the PrP res molecular profile are not necessarily associated with changes in their biological properties [133].…”

Section: Biological Properties Of Cell-passaged Prion Strainsmentioning

confidence: 99%

Cell models of prion infection

Vilette

2007

Vet. Res.

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-Due to recent renewal of interest and concerns in prion diseases, a number of cell systems permissive to prion multiplication have been generated in the last years. These include established cell lines, neuronal stem cells and primary neuronal cultures. While most of these models are permissive to experimental, mouse-adapted strains of prions, the propagation of natural field isolates from sheep scrapie and chronic wasting disease has been recently achieved. These models have improved our knowledge on the molecular and cellular events controlling the conversion of the PrP C protein into abnormal isoforms and on the cell-to-cell spreading of prions. Infected cultured cells will also facilitate investigations on the molecular basis of strain identity and on the mechanisms that lead to neurodegeneration. The ongoing development of new cell models with improved characteristics will certainly be useful for a number of unanswered critical issues in the prion field.

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Prions

Béringue

2015

Reviews in Cell Biology and Molecular Medicine

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Cultured Peripheral Neuroglial Cells Are Highly Permissive to Sheep Prion Infection

Cited by 80 publications

References 63 publications

Prions can infect primary cultured neurons and astrocytes and promote neuronal cell death

Prions can infect primary cultured neurons and astrocytes and promote neuronal cell death

Cell models of prion infection

Prions

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