Transcriptomic Determinants of Scrapie Prion Propagation in Cultured Ovine Microglia.
Susceptibility to infection by prions is highly dependent on the amino acid sequence and host expression of the cellular prion protein (PrPC); however, cellular expression of a genetically susceptible PrPC is insufficient. As an example, it has been shown in cultured cells that permissive and resist...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4726464?pdf=render |
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| author | Juan F Muñoz-Gutiérrez Sebastián Aguilar Pierlé David A Schneider Timothy V Baszler James B Stanton |
| author_facet | Juan F Muñoz-Gutiérrez Sebastián Aguilar Pierlé David A Schneider Timothy V Baszler James B Stanton |
| author_sort | Juan F Muñoz-Gutiérrez |
| collection | DOAJ |
| description | Susceptibility to infection by prions is highly dependent on the amino acid sequence and host expression of the cellular prion protein (PrPC); however, cellular expression of a genetically susceptible PrPC is insufficient. As an example, it has been shown in cultured cells that permissive and resistant sublines derived from the same parental population often have similar expression levels of PrPC. Thus, additional cellular factors must influence susceptibility to prion infection. The aim of this study was to elucidate the factors associated with relative permissiveness and resistance to scrapie prions in cultured cells derived from a naturally affected species. Two closely related ovine microglia clones with different prion susceptibility, but no detectable differences in PrPC expression levels, were inoculated with either scrapie-positive or scrapie-negative sheep brainstem homogenates. Five passages post-inoculation, the transcriptional profiles of mock and infected clones were sequenced using Illumina technology. Comparative transcriptional analyses identified twenty-two differentially transcribed genes, most of which were upregulated in poorly permissive microglia. This included genes encoding for selenoprotein P, endolysosomal proteases, and proteins involved in extracellular matrix remodeling. Furthermore, in highly permissive microglia, transforming growth factor β-induced, retinoic acid receptor response 1, and phosphoserine aminotranspherase 1 gene transcripts were upregulated. Gene Set Enrichment Analysis identified proteolysis, translation, and mitosis as the most affected pathways and supported the upregulation trend of several genes encoding for intracellular proteases and ribosomal proteins in poorly permissive microglia. This study identifies new genes potentially involved in scrapie prion propagation, corroborates results from other studies, and extends those results into another cell culture model. |
| first_indexed | 2024-12-10T18:28:49Z |
| format | Article |
| id | doaj.art-bf6bef99e2df426c855df90d07cdd0bd |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T18:28:49Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-bf6bef99e2df426c855df90d07cdd0bd2022-12-22T01:38:00ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01111e014772710.1371/journal.pone.0147727Transcriptomic Determinants of Scrapie Prion Propagation in Cultured Ovine Microglia.Juan F Muñoz-GutiérrezSebastián Aguilar PierléDavid A SchneiderTimothy V BaszlerJames B StantonSusceptibility to infection by prions is highly dependent on the amino acid sequence and host expression of the cellular prion protein (PrPC); however, cellular expression of a genetically susceptible PrPC is insufficient. As an example, it has been shown in cultured cells that permissive and resistant sublines derived from the same parental population often have similar expression levels of PrPC. Thus, additional cellular factors must influence susceptibility to prion infection. The aim of this study was to elucidate the factors associated with relative permissiveness and resistance to scrapie prions in cultured cells derived from a naturally affected species. Two closely related ovine microglia clones with different prion susceptibility, but no detectable differences in PrPC expression levels, were inoculated with either scrapie-positive or scrapie-negative sheep brainstem homogenates. Five passages post-inoculation, the transcriptional profiles of mock and infected clones were sequenced using Illumina technology. Comparative transcriptional analyses identified twenty-two differentially transcribed genes, most of which were upregulated in poorly permissive microglia. This included genes encoding for selenoprotein P, endolysosomal proteases, and proteins involved in extracellular matrix remodeling. Furthermore, in highly permissive microglia, transforming growth factor β-induced, retinoic acid receptor response 1, and phosphoserine aminotranspherase 1 gene transcripts were upregulated. Gene Set Enrichment Analysis identified proteolysis, translation, and mitosis as the most affected pathways and supported the upregulation trend of several genes encoding for intracellular proteases and ribosomal proteins in poorly permissive microglia. This study identifies new genes potentially involved in scrapie prion propagation, corroborates results from other studies, and extends those results into another cell culture model.http://europepmc.org/articles/PMC4726464?pdf=render |
| spellingShingle | Juan F Muñoz-Gutiérrez Sebastián Aguilar Pierlé David A Schneider Timothy V Baszler James B Stanton Transcriptomic Determinants of Scrapie Prion Propagation in Cultured Ovine Microglia. PLoS ONE |
| title | Transcriptomic Determinants of Scrapie Prion Propagation in Cultured Ovine Microglia. |
| title_full | Transcriptomic Determinants of Scrapie Prion Propagation in Cultured Ovine Microglia. |
| title_fullStr | Transcriptomic Determinants of Scrapie Prion Propagation in Cultured Ovine Microglia. |
| title_full_unstemmed | Transcriptomic Determinants of Scrapie Prion Propagation in Cultured Ovine Microglia. |
| title_short | Transcriptomic Determinants of Scrapie Prion Propagation in Cultured Ovine Microglia. |
| title_sort | transcriptomic determinants of scrapie prion propagation in cultured ovine microglia |
| url | http://europepmc.org/articles/PMC4726464?pdf=render |
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