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The Glycosylation Status of PrPC Is a Key Factor in Determining Transmissible Spongiform Encephalopathy Transmission between Species

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    Rights statement: Copyright © 2015, Wiseman et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 3.0 Unported license.

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http://jvi.asm.org/content/89/9/4738
Original languageEnglish
Pages (from-to)4738-4747
Number of pages10
JournalJournal of Virology
Volume89
Issue number9
DOIs
StatePublished - May 2015

Abstract

The risk of transmission of transmissible spongiform encephalopathies (TSE) between different species has been notoriously unpredictable because the mechanisms of transmission are not fully understood. A transmission barrier between species often prevents infection of a new host with a TSE agent. Nonetheless, some TSE agents are able to cross this barrier and infect new species, with devastating consequences. The host PrPC misfolds during disease pathogenesis and has a major role in controlling the transmission of agents between species, but sequence compatibility between host and agent PrPC does not fully explain host susceptibility. PrPC is posttranslationally modified by the addition of glycan moieties which have an important role in the infectious process. Here, we show in vivo that glycosylation of the host PrPC has a significant impact on the transmission of TSE between different host species. We infected mice carrying different glycosylated forms of PrPC with two human agents (sCJDMM2 and vCJD) and one hamster strain (263K). The absence of glycosylation at both or the first PrPC glycosylation site in the host results in almost complete resistance to disease. The absence of the second site of N-glycan has a dramatic effect on the barrier to transmission between host species, facilitating the transmission of sCJDMM2 to a host normally resistant to this agent. These results highlight glycosylation of PrPC as a key factor in determining the transmission efficiency of TSEs between different species.

    Research areas

  • CREUTZFELDT-JAKOB-DISEASE, HUMAN PRION PROTEIN, STRAIN VARIATION, VARIANT CJD, MOLECULAR-BASIS, SCRAPIE AGENT, N-TERMINUS, IN-VITRO, MICE, BRAIN

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