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    Artificial strain of human prions created in vitro

    Artificial strain of human prions created in vitro

    Tue, Jun 5, 2018 1:57 pm

    Terry Singeltary flounder9@verizon.netHide

    To bse-l bse-l@lists.aegee.org

    Cc cjd-l cjd-l@lists.aegee.org, cjdvoice cjdvoice@yahoogroups.com, bloodcjd bloodcjd@yahoogroups.com

    Published: 04 June 2018

    Artificial strain of human prions created in vitro

    Chae Kim, Xiangzhu Xiao, Shugui Chen, Tracy Haldiman, Vitautas Smirnovas, Diane Kofskey, Miriam Warren, Krystyna Surewicz, Nicholas R. Maurer, Qingzhong Kong, Witold Surewicz & Jiri G. Safar

    Nature Communicationsvolume 9, Article number: 2166 (2018)

    Abstract

    The molecular mechanism that determines under physiological conditions transmissibility of the most common human prion disease, sporadic Creutzfeldt-Jakob disease (sCJD) is unknown. We report the synthesis of new human prion from the recombinant human prion protein expressed in bacteria in reaction seeded with sCJD MM1 prions and cofactor, ganglioside GM1. These synthetic human prions were infectious to transgenic mice expressing non-glycosylated human prion protein, causing neurologic dysfunction after 459 and 224 days in the first and second passage, respectively. The neuropathology, replication potency, and biophysical profiling suggest that a novel, particularly neurotoxic human prion strain was created. Distinct biological and structural characteristics of our synthetic human prions suggest that subtle changes in the structural organization of critical domains, some linked to posttranslational modifications of the pathogenic prion protein (PrPSc), play a crucial role as a determinant of human prion infectivity, host range, and targetting of specific brain structures in mice models.


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