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Dernière mise à jour : Mai 2018

Menu Logo Principal AgroParisTech Université Paris-Saclay

INRA GABI Unit

GABI : Génétique Animale et Biologie IntégrativeUnité Mixte de Recherche INRA - AgroParisTech

The prion, a very discreet infectious agent

27 January 2012

INRA/VIM/Beringue
In mammals, the prion is responsible for the occurrence of transmissible spongiform encephalopathies or prion diseases that cause degeneration of the central nervous system of the infected host. A team of scientists from INRA has shown for the first time that while prion transmission across species may show no detectable sign of disease in brain, infection can burst in lymphatic tissues. These original results were published in the journal Science on 27 January 2012.

Like other pathogens (bacteria, viruses), prions can be transmissible between species, representing a risk to humans; for example, the variant form of Creutzfeldt-Jakob disease is caused by the ingestion of food contaminated by Bovine Spongiform Encephalopathy (BSE or mad cow disease) prions. The potential of prions to spread across species is limited by the so-called “species barrier”. When such cross-species contamination occurs, the absence of clinical signs and/or prions in the brain of infected individuals suggests a strong species barrier. While prions primarily replicate in the brain, the lymphoid tissue is known to be permissive to certain prions on transmission between two individuals of the same species. However, it is not clear whether different organs of a single individual are differentially permissive to foreign prions, due to distinct cell environments or intrinsic variations in the normal, cellular prion protein.

INRA scientists have studied the relative ability of the nervous and lymphoid tissues to replicate prions during apparently inefficient, interspecies transmissions (absence of clinical signs and prions in the majority of the experimentally infected animals). As a result, when prions originating from deer or cows were transmitted to mouse lines expressing human or ovine cellular prion proteins, they nearly exclusively multiplied in the lymphoid tissue, and relatively early with regard to the life-span of the animal. In one of the mouse models studied, the scientists further showed that when the species barrier was finally overcome through the emergence of a variant prion in the brain of the inoculated animals, a distinct agent propagated in the spleen, which could readily re-infect the initial host.

These results show that the ability of prion to spread and evolve between species is strongly tissue-dependent within a single host. In terms of public health, this work stresses the importance of studying more systematically extraneuronal tissues when evaluating animal prion potential to infect humans. In the light of this work, the species barrier between BSE prions and humans may be weaker than anticipated if the surveillance is focused solely on the central nervous system. It encourages the search for asymptomatic infected hosts through systematic screening of prions in the lymphoid tissue, as currently carried out in the UK. It may be important to pursue such screening policies on a long-term basis since this study suggests that prions can propagate silently for a long period of time in the lymphoid tissue, before being detectable by current diagnosis methods. Further research needs to be done on the factors determining host permissiveness to prions and their potential of adaptation.

*Molecular Virology and Immunology unit, Animal Genetics and Integrative Biology Joint Research Unit

Reference:

Béringue V, Herzog L, Jaumain E, Reine F, Sibille P, Le Dur A, Vilotte JL, Laude H: Facilitated cross-species transmission of prions in extraneural tissue. Science, 2012, DOI : 10.1126/science.1215659.

Site : The INRA Press Release