Neurotoxic Antibodies against the Prion Protein Do Not Trigger Prion Replication.
Prions are the infectious agents causing transmissible spongiform encephalopathies (TSE), progressive, inexorably lethal neurological diseases. Antibodies targeting the globular domain (GD) of the cellular prion protein PrPC trigger a neurotoxic syndrome morphologically and molecularly similar to pr...
| Main Authors: | , , , , , , , , |
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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/PMC5042507?pdf=render |
| _version_ | 1818984922649460736 |
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| author | Karl Frontzek Manuela Pfammatter Silvia Sorce Assunta Senatore Petra Schwarz Rita Moos Katrin Frauenknecht Simone Hornemann Adriano Aguzzi |
| author_facet | Karl Frontzek Manuela Pfammatter Silvia Sorce Assunta Senatore Petra Schwarz Rita Moos Katrin Frauenknecht Simone Hornemann Adriano Aguzzi |
| author_sort | Karl Frontzek |
| collection | DOAJ |
| description | Prions are the infectious agents causing transmissible spongiform encephalopathies (TSE), progressive, inexorably lethal neurological diseases. Antibodies targeting the globular domain (GD) of the cellular prion protein PrPC trigger a neurotoxic syndrome morphologically and molecularly similar to prion disease. This phenomenon raises the question whether such antibodies induce infectious prions de novo. Here we exposed cerebellar organotypic cultured slices (COCS) to the neurotoxic antibody, POM1. We then inoculated COCS homogenates into tga20 mice, which overexpress PrPC and are commonly utilized as sensitive indicators of prion infectivity. None of the mice inoculated with COCS-derived lysates developed any signs of disease, and all mice survived for at least 200 days post-inoculation. In contrast, all mice inoculated with bona fide prions succumbed to TSE after 55-95 days. Post-mortem analyses did not reveal any signs of prion pathology in mice inoculated with POM1-COCS lysates. Also, lysates from POM1-exposed COCS were unable to convert PrP by quaking. Hence, anti-GD antibodies do not catalyze the generation of prion infectivity. These data indicate that prion replication can be separated from prion toxicity, and suggest that anti-GD antibodies exert toxicity by acting downstream of prion replication. |
| first_indexed | 2024-12-20T18:26:42Z |
| format | Article |
| id | doaj.art-375f6c4ea4064a5e80ebc999936eb25c |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T18:26:42Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-375f6c4ea4064a5e80ebc999936eb25c2022-12-21T19:30:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01119e016360110.1371/journal.pone.0163601Neurotoxic Antibodies against the Prion Protein Do Not Trigger Prion Replication.Karl FrontzekManuela PfammatterSilvia SorceAssunta SenatorePetra SchwarzRita MoosKatrin FrauenknechtSimone HornemannAdriano AguzziPrions are the infectious agents causing transmissible spongiform encephalopathies (TSE), progressive, inexorably lethal neurological diseases. Antibodies targeting the globular domain (GD) of the cellular prion protein PrPC trigger a neurotoxic syndrome morphologically and molecularly similar to prion disease. This phenomenon raises the question whether such antibodies induce infectious prions de novo. Here we exposed cerebellar organotypic cultured slices (COCS) to the neurotoxic antibody, POM1. We then inoculated COCS homogenates into tga20 mice, which overexpress PrPC and are commonly utilized as sensitive indicators of prion infectivity. None of the mice inoculated with COCS-derived lysates developed any signs of disease, and all mice survived for at least 200 days post-inoculation. In contrast, all mice inoculated with bona fide prions succumbed to TSE after 55-95 days. Post-mortem analyses did not reveal any signs of prion pathology in mice inoculated with POM1-COCS lysates. Also, lysates from POM1-exposed COCS were unable to convert PrP by quaking. Hence, anti-GD antibodies do not catalyze the generation of prion infectivity. These data indicate that prion replication can be separated from prion toxicity, and suggest that anti-GD antibodies exert toxicity by acting downstream of prion replication.http://europepmc.org/articles/PMC5042507?pdf=render |
| spellingShingle | Karl Frontzek Manuela Pfammatter Silvia Sorce Assunta Senatore Petra Schwarz Rita Moos Katrin Frauenknecht Simone Hornemann Adriano Aguzzi Neurotoxic Antibodies against the Prion Protein Do Not Trigger Prion Replication. PLoS ONE |
| title | Neurotoxic Antibodies against the Prion Protein Do Not Trigger Prion Replication. |
| title_full | Neurotoxic Antibodies against the Prion Protein Do Not Trigger Prion Replication. |
| title_fullStr | Neurotoxic Antibodies against the Prion Protein Do Not Trigger Prion Replication. |
| title_full_unstemmed | Neurotoxic Antibodies against the Prion Protein Do Not Trigger Prion Replication. |
| title_short | Neurotoxic Antibodies against the Prion Protein Do Not Trigger Prion Replication. |
| title_sort | neurotoxic antibodies against the prion protein do not trigger prion replication |
| url | http://europepmc.org/articles/PMC5042507?pdf=render |
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