Accelerated, spleen-based titration of variant CJD infectivity in transgenic mice expressing human prion protein with sensitivity comparable to survival time bioassay
Accelerated, spleen-based titration of variant CJD infectivity in
transgenic mice expressing human prion protein with sensitivity comparable to
survival time bioassay
Sophie Halliez1, Fabienne Reine1, Laetitia Herzog1, Emilie Jaumain1,
Stéphane Haïk2,3,4, Human Rezaei1, Jean-Luc Vilotte5, Hubert Laude1 and Vincent
Béringue1*
+ Author Affiliations 1INRA (institut National de la Recherche
Agronomique), UR892, Virologie Immunologie Moléculaires, F-78350 Jouy-en-Josas,
France 2INSERM, Equipe maladie d'Alzheimer et maladies à Prions, CRicm, UMRS
975, CNRS UMR7225, UPMC. R., Hôpital de la Salpêtrière, F-75013, Paris, France.
3InVS, Centre national de référence des Agents Transmissibles Non
Conventionnels, Hôpital de la Salpêtrière, F-75013, Paris, France. 4AP-HP,
Laboratoire de Neuropathologie, Hôpital de la Salpêtrière, F-75013, Paris,
France 5INRA, UMR1313, Génétique Animale et Biologie Intégrative, F-78350
Jouy-en-Josas, France
ABSTRACT
The dietary exposure of the human population to the prions responsible for
the bovine spongiform encephalopathy (BSE) epizooty has led to the emergence of
variant Creutzfeldt-Jakob disease (vCJD). This fatal, untreatable
neurodegenerative disorder is a growing public health concern because the
prevalence of the infection seems much greater than the disease incidence and
because secondary transmission of vCJD by blood transfusion or use of blood
products has occurred. A current limitation in variant CJD risk assessment
purposes is the lack of quantitative information on the infectivity of
contaminated tissues. To these aims, we tested the potential of a transgenic
mouse line overexpressing human PrP, which was previously reported to propagate
vCJD prions. Endpoint titration of vCJD infectivity in different tissues was
evaluated by two different methods: i) the “classical” bioassay, based on the
appearance of clinical symptoms and the detection of pathological prion protein
in tissues of the inoculated mouse, ii) a shortened bioassay based on the
detection of the protein in the mouse spleen at defined time points. Both
methods proved equally sensitive in quantifying infectivity, even after very low
dose inoculation of infected material, but the time time-schedule was shortened
from ∼2.5-year to ∼1-year with the spleen bioassay. Compared to the
‘gold-standard’ RIII model routinely used for endpoint titration of vCJD/BSE
prions, either method improved the sensitivity by >2 orders of magnitude and
allowed re-evaluating the infectious titre of spleen from a vCJD individual at
disease end stage to >1000-fold higher values.
Importance Here, we provide key re-evaluation of the infectious titre of
variant CJD brain and spleen tissues. The highly sensitive, accelerated
spleen-based assay should thus constitute a key advance for variant CJD
epidemiological and risk assessment purposes and should greatly facilitate
future titration studies, aimed at validating decontamination procedures for
example. The overlooked notion that the lymphoid tissue exhibits higher capacity
than the brain to replicate prions even after low dose infection raises new
questions about the molecular and/or cellular determinant(s) involved, a key
issue regarding potent silent carriers of variant CJD in the lymphoid tissue.
FOOTNOTES ↵* Corresponding author: vincent.beringue@jouy.inra.fr Copyright
© 2014, American Society for Microbiology. All Rights Reserved.
CANADA SEE STEADY INCREASE OF THE SPORADIC CJD’S AND THE VPSPR’S (sporadic
CJD’s). ...tss
PLEASE NOTE, type determination pending Creutzfeldt Jakob Disease (tdpCJD)
in Canada is also on a steady increase.
please see ;
> 3. Final classification of 50 cases from 2009, 2010, 2011 and 2012 is
pending.
CJD Deaths Reported by CJDSS1, 1994-20122
CJD Deaths Reported by CJDSS1, 1994-20122
As of May 31, 2012
SEE DECEMBER 2012 CANADA
USA SEE STEADY INCREASE OF THE SPORADIC CJD’S AND THE VPSPR’S (sporadic
CJD’s). ...tss
National Prion Disease Pathology Surveillance Center
Cases Examined1
(May 18, 2012)
5 Includes 14 cases in which the diagnosis is pending, and 18 inconclusive
cases;
6 Includes 17 (16 from 2012) cases with type determination pending in which
the diagnosis of vCJD has been excluded. The Sporadic cases include 16 cases of
sporadic Fatal Insomnia (sFI) and 42 cases of Variably Protease-Sensitive
Prionopathy (VPSPr) and 2118 cases of sporadic Creutzfeldt-Jakob disease (sCJD).
Rev 5/18/2012
> 6 Includes
> 17 (16 from 2012) cases with type determination pending in which the
diagnosis of vCJD has been excluded.
> The Sporadic cases include 16 cases of sporadic Fatal Insomnia (sFI)
and 42 cases of Variably Protease-Sensitive Prionopathy (VPSPr) and 2118 cases
of sporadic Creutzfeldt-Jakob disease (sCJD).
WELL, it seems the USA mad cow strains in humans classified as type
determination pending tdpCJD, VPSPr, sFFI, and sCJD) have steadily increased
over the years, and the same old song and dance continues with sporadic CJD
cases $$$
Creutzfeldt-Jakob Disease CJD cases rising North America updated report
August 2013
*** Creutzfeldt-Jakob Disease CJD cases rising North America with Canada
seeing an extreme increase of 48% between 2008 and 2010 ***
Sunday, October 13, 2013
*** CJD TSE Prion Disease Cases in Texas by Year, 2003-2012
Tuesday, April 01, 2014
Questions linger in U.S. CJD cases 2005, and still do in 2014
Sunday, March 09, 2014
A Creutzfeldt-Jakob Disease (CJD) Lookback Study: Assessing the Risk of
Blood Borne Transmission of Classic Forms of Creutzfeldt-Jakob Disease
FDA TSEAC CIRCUS AND TRAVELING ROAD SHOW FOR THE TSE PRION DISEASES
Sunday, April 06, 2014
SPORADIC CJD and the potential for zoonotic transmission there from, either
directly or indirectly via friendly fire iatrogenic mode, evidence to date
Wednesday, December 11, 2013
*** Detection of Infectivity in Blood of Persons with Variant and Sporadic
Creutzfeldt-Jakob Disease ***
Friday, April 25, 2014
Accuracy of administrative diagnostic data for pathologically confirmed
cases of Creutzfeldt-Jakob disease in Massachusetts, 2000-2008
Article in Press
Monday, May 19, 2014
Variant CJD: 18 years of research and surveillance
TSS
posted by Terry S. Singeltary Sr. | 10:39 AM
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