Prion protein amino acid sequence influences formation of authentic synthetic PrP(Sc).
Prion protein amino acid sequence influences formation of authentic synthetic PrP(Sc).
复制标题
DOI：
10.1038/s41598-022-26300-0
复制
发表时间：
2023-01-09
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
合成朊病毒，从最小的，非传染性的成分从头产生，在动物中引起真正的朊病毒疾病。合成朊病毒传播到表达同源PrPC的宿主会导致潜伏期延长、变异和不完全攻击率。相比之下，通过PMCA产生的小鼠合成朊病毒（MSP）与最小的辅因子容易感染小鼠和仓鼠，并迅速适应这两个物种。为了研究在与MSP相同的条件下产生的仓鼠合成朊病毒（HSP）是否也具有高度感染性，我们用仓鼠野生型或突变型（ΔG54，ΔG54/M139 I，M139 I/I205 M）重组PrP产生的HSP接种仓鼠。接种的仓鼠均未出现朊病毒病的临床体征，然而，来自HSPWT和HSPΔG54感染仓鼠的脑匀浆含有PrPSc，表明亚临床感染。仓鼠的连续传代导致第二次传代时出现临床疾病，并伴有第二次和第三次传代之间潜伏期和PrPSc构象稳定性的变化。这些数据表明HSP与MSP相反，不包含PrPSc，而是通过变形模板生成真实的PrPSc。MSP和HSP之间的感染性差异表明，在相似的生成条件下，PrP的氨基酸序列影响正宗PrPSc的生成。
Synthetic prions, generated de novo from minimal, non-infectious components, cause bona fide prion disease in animals. Transmission of synthetic prions to hosts expressing syngeneic PrPC results in extended, variable incubation periods and incomplete attack rates. In contrast, murine synthetic prions (MSP) generated via PMCA with minimal cofactors readily infected mice and hamsters and rapidly adapted to both species. To investigate if hamster synthetic prions (HSP) generated under the same conditions as the MSP are also highly infectious, we inoculated hamsters with HSP generated with either hamster wild type or mutant (ΔG54, ΔG54/M139I, M139I/I205M) recombinant PrP. None of the inoculated hamsters developed clinical signs of prion disease, however, brain homogenate from HSPWT- and HSPΔG54-infected hamsters contained PrPSc, indicating subclinical infection. Serial passage in hamsters resulted in clinical disease at second passage accompanied by changes in incubation period and PrPSc conformational stability between second and third passage. These data suggest the HSP, in contrast to the MSP, are not comprised of PrPSc, and instead generate authentic PrPSc via deformed templating. Differences in infectivity between the MSP and HSP suggest that, under similar generation conditions, the amino acid sequence of PrP influences generation of authentic PrPSc.
登录
查看更多内容
影响因子：
6.7
作者：
Wang X;McGovern G;Zhang Y;Wang F;Zha L;Jeffrey M;Ma J
通讯作者：
Ma J
影响因子：
6.7
作者：
Colby DW;Wain R;Baskakov IV;Legname G;Palmer CG;Nguyen HO;Lemus A;Cohen FE;DeArmond SJ;Prusiner SB
通讯作者：
Prusiner SB
影响因子：
4.6
作者：
Katorcha E;Makarava N;Savtchenko R;Baskakov IV
通讯作者：
Baskakov IV
影响因子：
5.6
作者：
Kaneko, K;Ball, HL;Cohen, FE
通讯作者：
Cohen, FE
DOI：
10.1073/pnas.0706522104
发表时间：
2007-11-27
影响因子：
11.1
作者：
Cobb, Nathan J.;Soennichsen, Frank D.;Surewicz, Witold K.
通讯作者：
Surewicz, Witold K.