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A new form of prion replication is described that might explain some transmission barriers

Part of the in vivo experiments of this international study were performed in IRTA-CReSA level 3 biocontainment facility

A new form of prion replication is described for the first time in a study recently published in the journal Proceedings of the National Academy of Sciences (PNAS) in which prions are able to propagate in the new host but are not adapted and preserve Its original characteristics: NAPA or non-adaptive prion amplification.

A considerable part of the in vivo experiments with mice of this study have been carried out in IRTA-CReSA’s  level 3 biocontainment unit and in PRIOCAT laboratory, both  meet the biosecurity conditions necessary to work with these infectious agents. This unit of biocontention is part of the RELASB, the network of high biological safety laboratories in the map of Unique Scientific and Technical Infrastructures (ICTS) in Spain.

The in vitro experiments were carried out by the group of Dr. Joaquin Castilla of the CICbioGUNE in Bilbao. The study was led by the group of Dr. Glenn Telling of the Colorado Prion Research Center (PRC) in the United States and included the collaboration of other US and Italian groups.

The study describes, among other examples, how scrapie prions (a TSE affecting sheep) can be replicated inefficiently in transgenic mice that have the prion protein of the horse and yet are unable to adapt and continue to propagate in this species. Instead, they can be replicated efficiently in a mouse that expresses the sheep prion protein. That is, they retain the properties of the original inoculum.

The study has also shown, for the first time, that horses are resistant to infection by several different strains of prions. It seems that this is due to a special conformation of its prion protein.

Autor: Enric Vidal Figure: Some of the experiments performed with transgenic mice expressing the horse prion protein. Scrapie is able to propagate in these mice, but it does not adapt. Instead it retains the ability to efficiently infect mice that express the sheep prion protein. Legend: arrows represent intracerebral inoculations. Gray: no transmission. Orange: inefficient transmission. Red: efficient transmission

This new model of prion replication has also been observed in Transmissible Mink Encephalopathy (TME) transmission experiments in transgenic mice expressing the deer prion protein.

Interestingly, this model could explain the inefficient transmission of BSE, Bovine Spongiform Encephalopathy or mad cow disease, to humans … the hypothesis is that this was another case of NAPA. Humans can be infected with BSE but this prion does not adapt to our species. Perhaps that is why despite having been exposed to BSE prions the number of vCJD cases in people has been relatively small.

Autor: Enric Vidal Figure : Hypothesis, based on results of experiments with transgenic mice expressing cattle or human prion protein and postulating that BSE has not adapted to the human species, but is able to amplify and accumulate itself. vCJD: Variant of Creutzfeldt Jakob disease (caused in people by ingestion of prions of mad cow). Legend: arrows represent intracerebral inoculations. Orange: inefficient transmission. Red: efficient transmission

For more information, you can read the post by Dr. Vidal at IRTA-CReSA’s animal science divulgation blog: CReSA & the City.

Full paper:

Prion replication without host adaptation during interspecies transmissions PNAS 2017 Jifeng Bian, Vadim Khaychuk, Rachel C. Angers, Natalia Fernández-Borges, Enric Vidal, Crystal Meyerett-Reid, Sehun Kim, Carla Calvi, Jason C. Bartz, Edward A. Hoover, Umberto Agrimi, Jürgen A. Richt, Joaquín Castilla, and Glenn C. Telling