Abstract
Cynomolgus macaque has been used for the evaluation of the zoonotic potential of prion diseases, especially for classical-Bovine Spongiform Encephalopathy (classical-BSE) infectious agent. PrP amino acid sequence is considered to play a key role in the susceptibility to prion strains and only one amino acid change may alter this susceptibility. Macaque and human-PrP sequences have only nine amino acid differences, but the effect of these amino acid changes in the susceptibility to dissimilar prion strains is unknown. In this work, the transmissibility of a panel of different prions from several species was compared in transgenic mice expressing either macaque-PrPC (TgMac) or human-PrPC (Hu-Tg340). Similarities in the transmissibility of most prion strains were observed suggesting that macaque is an adequate model for the evaluation of human susceptibility to most of the prion strains tested. Interestingly, TgMac were more susceptible to classical-BSE strain infection than Hu-Tg340. This differential susceptibility to classical-BSE transmission should be taken into account for the interpretation of the results obtained in macaques. It could notably explain why the macaque model turned out to be so efficient (worst case model) until now to model human situation towards classical-BSE despite the limited number of animals inoculated in the laboratory experiments.
Highlights
Cynomolgus macaque has been used for the evaluation of the zoonotic potential of prion diseases, especially for classical-Bovine Spongiform Encephalopathy infectious agent
While PrP amino acid sequence seems to play a key role in prion transmission susceptibility, host factors other than PrPC can modulate prion strain features[7,8]
The nine amino acid differences between human and macaque PrP may alter prion susceptibility of these two species. We address this question comparing the susceptibility of transgenic mouse models expressing either human or macaque PrP when inoculated with a panel of diverse prions
Summary
Cynomolgus macaque has been used for the evaluation of the zoonotic potential of prion diseases, especially for classical-Bovine Spongiform Encephalopathy (classical-BSE) infectious agent. Several studies have been done using non-human primates to study the transmissibility of prion diseases[17,18] and more recently, macaque monkeys have been widely used for prion disease transmissions[19,20,21,22,23,24,25,26,27,28,29,30] In this sense, non-human primates are considered to be the ultimate model of the human condition with regard to prions, especially for BSE infection[19,22]. Non-human primates are considered to be the ultimate model of the human condition with regard to prions, especially for BSE infection[19,22] Both macaque and human PrP amino acid sequences are quite similar, but only one amino acid change may alter susceptibility to prions drastically, as occurs with the Met/Val 129 dimorphism in human PrP sequence for classical-BSE prion strain[14].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
