Abstract
BackgroundThe 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.Methodology/Principal FindingsTransgenic 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.Conclusion/SignificanceOur findings emphasize the possibility that human-to-human transmission of vCJD might produce alternative neuropathogical 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.
Highlights
The variant form of CJD, thought to have arisen from exposure of the population to cattle BSE-contaminated food [1,2], is perceived as the most threatening to public health among the human prion diseases [3]
BSE/variant form of CJD (vCJD) transmission studies in macaques suggested an increased virulence of the host-adapted agent [12], as generally observed when prions cross a species barrier. For all these reasons and the recent reporting of four vCJD cases associated to blood transfusion [13,14,15], the extend of the iatrogenic risk associated with subclinical vCJD infection needs to be assessed more precisely
We show that infection in these mice closely parallels vCJD infection in humans with enhanced tropism for lymphoreticular tissues compared to sporadic CJD (sCJD) agent, providing a potentially relevant model to investigate the peripheral propagation of vCJD at different stages of the incubation
Summary
The variant form of CJD (vCJD), thought to have arisen from exposure of the population to cattle BSE-contaminated food [1,2], is perceived as the most threatening to public health among the human prion diseases [3]. 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. Our findings emphasize the possibility that human-to-human transmission of vCJD might produce alternative neuropathogical phenotypes and that lymphoid tissue examination of CJD cases classified as sporadic might reveal an infection by vCJD-type prions They provide evidence for the strong propensity of this agent to establish long-lasting, subclinical vCJD infection of lymphoreticular tissues, amplifying the risk for iatrogenic transmission
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
