Accelerated High Fidelity Prion Amplification Within and Across Prion Species Barriers

PLoS Pathogens

Kristi M. Green¹  Glenn C. Telling¹  Claudio Soto²  Joaquín Castilla²  Jean E. Jewell³  Tanya S. Seward⁴  Dana L. Napier⁴ 

[1] Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, Kentucky, United States of America;Department of Neurology, University of Texas Medical Branch, Galveston, Texas, United States of America;Department of Veterinary Sciences, University of Wyoming, Laramie, Wyoming, United States of America;Sanders Brown Center on Aging, University of Kentucky, Lexington, Kentucky, United States of America

关键词: Animal prion diseases;    Chronic wasting disease;    Prion diseases;    Brain diseases;    Mouse models;    Deer;    Central nervous system;    Scrapie;   

DOI  :  10.1371/journal.ppat.1000139

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Experimental obstacles have impeded our ability to study prion transmission within and, more particularly, between species. Here, we used cervid prion protein expressed in brain extracts of transgenic mice, referred to as Tg(CerPrP), as a substrate for in vitro generation of chronic wasting disease (CWD) prions by protein misfolding cyclic amplification (PMCA). Characterization of this infectivity in Tg(CerPrP) mice demonstrated that serial PMCA resulted in the high fidelity amplification of CWD prions with apparently unaltered properties. Using similar methods to amplify mouse RML prions and characterize the resulting novel cervid prions, we show that serial PMCA abrogated a transmission barrier that required several hundred days of adaptation and subsequent stabilization in Tg(CerPrP) mice. While both approaches produced cervid prions with characteristics distinct from CWD, the subtly different properties of the resulting individual prion isolates indicated that adaptation of mouse RML prions generated multiple strains following inter-species transmission. Our studies demonstrate that combined transgenic mouse and PMCA approaches not only expedite intra- and inter-species prion transmission, but also provide a facile means of generating and characterizing novel prion strains.

【 授权许可】

CC BY