Division of Molecular Neurobiology, Institute for Enzyme Research (KOSOKEN), Tokushima University, Kuramoto 3-18-15, Tokushima, 770-8503, Japan.
Division of Enzyme Chemistry, Institute for Enzyme Research (KOSOKEN), Tokushima University, Kuramoto 3-18-15, Tokushima, 770-8503, Japan.
Sci Rep. 2021 May 12;11(1):10109. doi: 10.1038/s41598-021-89586-6.
Misfolding of the cellular prion protein, PrP, into the amyloidogenic isoform, PrP, which forms infectious protein aggregates, the so-called prions, is a key pathogenic event in prion diseases. No pathogens other than prions have been identified to induce misfolding of PrP into PrP and propagate infectious prions in infected cells. Here, we found that infection with a neurotropic influenza A virus strain (IAV/WSN) caused misfolding of PrP into PrP and generated infectious prions in mouse neuroblastoma cells through a hit-and-run mechanism. The structural and biochemical characteristics of IAV/WSN-induced PrP were different from those of RML and 22L laboratory prions-evoked PrP, and the pathogenicity of IAV/WSN-induced prions were also different from that of RML and 22L prions, suggesting IAV/WSN-specific formation of PrP and infectious prions. Our current results may open a new avenue for the role of viral infection in misfolding of PrP into PrP and formation of infectious prions.
细胞朊病毒蛋白（PrP）错误折叠成淀粉样蛋白构象，形成感染性蛋白聚集体，即所谓的朊病毒，是朊病毒病的关键致病事件。除了朊病毒之外，没有其他病原体被确定可以诱导 PrP 错误折叠成 PrP，并在感染细胞中传播感染性朊病毒。在这里，我们发现，感染神经亲和性流感 A 病毒株（IAV/WSN）通过“打了就跑”机制导致 PrP 错误折叠成 PrP，并在小鼠神经母细胞瘤细胞中产生感染性朊病毒。IAV/WSN 诱导的 PrP 的结构和生化特征与 RML 和 22L 实验室诱导的 PrP 不同，IAV/WSN 诱导的朊病毒的致病性也与 RML 和 22L 朊病毒不同，表明 IAV/WSN 特异性形成 PrP 和感染性朊病毒。我们目前的结果可能为病毒感染在 PrP 错误折叠成 PrP 和形成感染性朊病毒中的作用开辟了新的途径。
