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Like other pathogens (bacteria, viruses), prions may transmit from one species to another, representing a risk to humans; for example, the variant form of Creutzfeldt-Jakob disease is linked to the ingestion of food contaminated by Bovine Spongiform Encephalopathy (BSE or mad cow disease) prions. Prion cross-species transmission abilities are usually limited by a barrier, commonly referred to as “species barrier”. Following experimental cross-species contamination, the absence of clinical signs and/or prions in the infected individual brain 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. Though, it is not clear whether different organs of a single individual are differentially permissive to foreign prions, due to distinct cell environment or intrinsic variations in the normal, cellular prion protein.

Prion replication in mouse spleen (obs. by immunofluorescence) Green=prion, Red= spleen B cells © INRA/VIM/Béringue

INRA scientists have studied the relative ability of the nervous and lymphoid tissue 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 quasi exclusively multiplied in the lymphoid tissue, and relatively early on. 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(2) in the brain of the inoculated animals, a distinct agent propagated in the spleen, which was able to readily re-infect the initial host.

These results show that prion ability 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 policy on a long-term basis as 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 host permissiveness determinism to prions and their potential of adaptation.

(1) Lymphatic tissues: organs that produce cells of the immune system (thymus, bone marrow, spleen, lymph nodes)

(2) Variant prion: a prion with new strain characteristics

* Molecular Virology and Immunology Research Unit

Reference and comments:

Facilitated cross-species transmission of prions in extraneural tissue. Science, 27 January 2012.
Vincent Béringue, Laëtitia Herzog, Emilie Jaumain, Fabienne Reine, Pierre Sibille, Annick Le Dur, Jean-Luc Vilotte and Hubert Laude.

The risk of prion zoonoses. Science, 27 January 2012. Perspectives. John Collinge

Prion diseases hide out in the spleen. Nature, 26 January 2012. News. Jo Merchant.