Mammalian prion propagation in PrP transgenic Drosophila.
Mammalian prion propagation in PrP transgenic Drosophila.
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DOI：
10.1093/brain/awy183
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发表时间：
2018-09-01
期刊：
影响因子：
--
通讯作者：
Bujdoso R
中科院分区：
文献类型：
--
作者：
Thackray AM;Andréoletti O;Bujdoso R
Thackray等人显示了哺乳动物朊病毒在仅对PrP转基因的黑腹果蝇（Drosophila melanogaster）中的真实繁殖。因此，株特异性朊病毒传播所需的分子和细胞辅因子并非哺乳动物所独有，这表明果蝇也可能是研究朊病毒传播的合适宿主。哺乳动物朊病毒通过正常细胞朊病毒相关蛋白PrPC的模板定向错误折叠和聚集繁殖，因为它转化为统称为PrPSc的疾病相关构象异构体。哺乳动物物种可能对朊病毒病是宽容的，因为这些宿主具有共同进化的特异性辅助因子，有助于PrPC构象变化和朊病毒繁殖。我们已经测试了这一假设，通过检查是否发生在正常的朊病毒零无脊椎动物宿主果蝇的忠实朊病毒传播。绵羊PrP转基因果蝇在幼虫期暴露于绵羊瘙痒病表现出传播性朊病毒在成年果蝇中的逐步积累。引人注目的是，不同的绵羊朊病毒株的生物学特性在果蝇中的繁殖过程中得到了保持。我们的观察表明，株特异性朊病毒繁殖所需的辅助因子不是哺乳动物物种所独有的。我们的研究确立了果蝇作为研究可传播哺乳动物朊病毒的新宿主。
Thackray et al. show authentic propagation of mammalian prions in Drosophila melanogaster rendered transgenic solely for PrP. The molecular and cellular co-factors necessary for strain-specific prion propagation are not therefore unique to mammals, suggesting that Drosophila may also be a suitable host for studying prion transmission. Mammalian prions propagate by template-directed misfolding and aggregation of normal cellular prion related protein PrPC as it converts into disease-associated conformers collectively referred to as PrPSc. Mammalian species may be permissive for prion disease because these hosts have co-evolved specific co-factors that assist PrPC conformational change and prion propagation. We have tested this hypothesis by examining whether faithful prion propagation occurs in the normally PrPC-null invertebrate host Drosophila melanogaster. Ovine PrP transgenic Drosophila exposed at the larval stage to ovine scrapie showed a progressive accumulation of transmissible prions in adult flies. Strikingly, the biological properties of distinct ovine prion strains were maintained during their propagation in Drosophila. Our observations show that the co-factors necessary for strain-specific prion propagation are not unique to mammalian species. Our studies establish Drosophila as a novel host for the study of transmissible mammalian prions.
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影响因子：
64.8
作者：
Moreno, Julie A.;Radford, Helois;Peretti, Diego;Steinert, Joern R.;Verity, Nicholas;Martin, Maria Guerra;Halliday, Mark;Morgan, Jason;Dinsdale, David;Ortori, Catherine A.;Barrett, David A.;Tsaytler, Pavel;Bertolotti, Anne;Willis, Anne E.;Bushell, Martin;Mallucci, Giovanna R.
通讯作者：
Mallucci, Giovanna R.
DOI：
10.1146/annurev.pathol.3.121806.151529
发表时间：
2009
期刊：
Annual review of pathology
影响因子：
--
作者：
Lu B;Vogel H
通讯作者：
Vogel H
影响因子：
3.5
作者：
Choi, Jin-Kyu;Jeon, Yong-Chul;Kim, Yong-Sun
通讯作者：
Kim, Yong-Sun
影响因子：
48
作者：
Atarashi, Ryuichiro;Moore, Roger A.;Caughey, Byron
通讯作者：
Caughey, Byron
影响因子：
11.4
作者：
Cancellotti, Enrico;Mahal, Sukhvir P.;Manson, Jean C.
通讯作者：
Manson, Jean C.