Prominent and persistent extraneural infection in human PrP transgenic mice infected with variant CJD.
<h4>Background</h4>The evolution of the variant Creutzfeldt-Jakob disease (vCJD) epidemic is hazardous to predict due to uncertainty in ascertaining the prevalence of infection and because the disease might remain asymptomatic or produce an alternate, sporadic-like phenotype.<h4>Me...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2008-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18183299/?tool=EBI |
| _version_ | 1819125781054357504 |
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| author | Vincent Béringue Annick Le Dur Philippe Tixador Fabienne Reine Laurence Lepourry Armand Perret-Liaudet Stéphane Haïk Jean-Luc Vilotte Michel Fontés Hubert Laude |
| author_facet | Vincent Béringue Annick Le Dur Philippe Tixador Fabienne Reine Laurence Lepourry Armand Perret-Liaudet Stéphane Haïk Jean-Luc Vilotte Michel Fontés Hubert Laude |
| author_sort | Vincent Béringue |
| collection | DOAJ |
| description | <h4>Background</h4>The evolution of the variant Creutzfeldt-Jakob disease (vCJD) epidemic is hazardous to predict due to uncertainty in ascertaining the prevalence of infection and because the disease might remain asymptomatic or produce an alternate, sporadic-like phenotype.<h4>Methodology/principal findings</h4>Transgenic mice were produced that overexpress human prion protein with methionine at codon 129, the only allele found so far in vCJD-affected patients. These mice were infected with prions derived from variant and sporadic CJD (sCJD) cases by intracerebral or intraperitoneal route, and transmission efficiency and strain phenotype were analyzed in brain and spleen. We showed that i) the main features of vCJD infection in humans, including a prominent involvement of the lymphoid tissues compared to that in sCJD infection were faithfully reproduced in such mice; ii) transmission of vCJD agent by intracerebral route could lead to the propagation of either vCJD or sCJD-like prion in the brain, whereas vCJD prion was invariably propagated in the spleen, iii) after peripheral exposure, inefficient neuroinvasion was observed, resulting in an asymptomatic infection with life-long persistence of vCJD prion in the spleen at stable and elevated levels.<h4>Conclusion/significance</h4>Our findings emphasize the possibility that human-to-human transmission of vCJD might produce alternative neuropathological phenotypes and that lymphoid tissue examination of CJD cases classified as sporadic might reveal an infection by vCJD-type prions. They also provide evidence for the strong propensity of this agent to establish long-lasting, subclinical vCJD infection of lymphoreticular tissues, thus amplifying the risk for iatrogenic transmission. |
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| id | doaj.art-e7f0eade8b06464f8dd4852ff4d632c8 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T07:45:35Z |
| publishDate | 2008-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-e7f0eade8b06464f8dd4852ff4d632c82022-12-21T18:33:39ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-01-0131e141910.1371/journal.pone.0001419Prominent and persistent extraneural infection in human PrP transgenic mice infected with variant CJD.Vincent BéringueAnnick Le DurPhilippe TixadorFabienne ReineLaurence LepourryArmand Perret-LiaudetStéphane HaïkJean-Luc VilotteMichel FontésHubert Laude<h4>Background</h4>The evolution of the variant Creutzfeldt-Jakob disease (vCJD) epidemic is hazardous to predict due to uncertainty in ascertaining the prevalence of infection and because the disease might remain asymptomatic or produce an alternate, sporadic-like phenotype.<h4>Methodology/principal findings</h4>Transgenic mice were produced that overexpress human prion protein with methionine at codon 129, the only allele found so far in vCJD-affected patients. These mice were infected with prions derived from variant and sporadic CJD (sCJD) cases by intracerebral or intraperitoneal route, and transmission efficiency and strain phenotype were analyzed in brain and spleen. We showed that i) the main features of vCJD infection in humans, including a prominent involvement of the lymphoid tissues compared to that in sCJD infection were faithfully reproduced in such mice; ii) transmission of vCJD agent by intracerebral route could lead to the propagation of either vCJD or sCJD-like prion in the brain, whereas vCJD prion was invariably propagated in the spleen, iii) after peripheral exposure, inefficient neuroinvasion was observed, resulting in an asymptomatic infection with life-long persistence of vCJD prion in the spleen at stable and elevated levels.<h4>Conclusion/significance</h4>Our findings emphasize the possibility that human-to-human transmission of vCJD might produce alternative neuropathological phenotypes and that lymphoid tissue examination of CJD cases classified as sporadic might reveal an infection by vCJD-type prions. They also provide evidence for the strong propensity of this agent to establish long-lasting, subclinical vCJD infection of lymphoreticular tissues, thus amplifying the risk for iatrogenic transmission.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18183299/?tool=EBI |
| spellingShingle | Vincent Béringue Annick Le Dur Philippe Tixador Fabienne Reine Laurence Lepourry Armand Perret-Liaudet Stéphane Haïk Jean-Luc Vilotte Michel Fontés Hubert Laude Prominent and persistent extraneural infection in human PrP transgenic mice infected with variant CJD. PLoS ONE |
| title | Prominent and persistent extraneural infection in human PrP transgenic mice infected with variant CJD. |
| title_full | Prominent and persistent extraneural infection in human PrP transgenic mice infected with variant CJD. |
| title_fullStr | Prominent and persistent extraneural infection in human PrP transgenic mice infected with variant CJD. |
| title_full_unstemmed | Prominent and persistent extraneural infection in human PrP transgenic mice infected with variant CJD. |
| title_short | Prominent and persistent extraneural infection in human PrP transgenic mice infected with variant CJD. |
| title_sort | prominent and persistent extraneural infection in human prp transgenic mice infected with variant cjd |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18183299/?tool=EBI |
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