PDF(Pubmed)
Abstract：
Accumulating evidence implicates that herpes simplex virus type 1 (HSV-1) has been linked to the development and progression of Alzheimer\'s disease (AD). HSV-1 infection induces β-amyloid (Aβ) deposition in vitro and in vivo, but the effect and precise mechanism remain elusive. Here, we show that HSV-1 infection of the brains of transgenic 5xFAD mice resulted in accelerated Aβ deposition, gliosis, and cognitive dysfunction. We demonstrate that HSV-1 infection induced the recruitment of microglia to the viral core to trigger microglial phagocytosis of HSV-GFP-positive neuronal cells. In addition, we reveal that the NLRP3 inflammasome pathway induced by HSV-1 infection played a crucial role in Aβ deposition and the progression of AD caused by HSV-1 infection. Blockade of the NLRP3 inflammasome signaling reduces Aβ deposition and alleviates cognitive decline in 5xFAD mice after HSV-1 infection. Our findings support the notion that HSV-1 infection is a key factor in the etiology of AD, demonstrating that NLRP3 inflammasome activation functions in the interface of HSV-1 infection and Aβ deposition in AD.
摘要：
越来越多的证据表明，单纯疱疹病毒1型（HSV-1）与阿尔茨海默病（AD）的发生和发展有关。HSV-1感染在体外和体内诱导β-淀粉样蛋白（Aβ）沉积，但是效果和确切的机制仍然难以捉摸。这里,我们表明，HSV-1感染转基因5xFAD小鼠的大脑导致加速的Aβ沉积，胶质增生,和认知功能障碍。我们证明HSV-1感染诱导小胶质细胞募集到病毒核心，以触发HSV-GFP阳性神经元细胞的小胶质细胞吞噬作用。此外,我们发现，HSV-1感染诱导的NLRP3炎性体通路在Aβ沉积和HSV-1感染引起的AD进展中起着至关重要的作用。在HSV-1感染后，NLRP3炎性体信号传导的阻断减少了Aβ沉积并减轻了5xFAD小鼠的认知下降。我们的研究结果支持以下观点：HSV-1感染是AD病因的关键因素。证明NLRP3炎性体激活在AD中HSV-1感染和Aβ沉积的界面中起作用。
