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Herpes simplex virus 1 accelerates the progression of Alzheimer's disease by modulating microglial phagocytosis and activating NLRP3 pathway
Zhimeng Wang # 1 2, Jing Liu # 3, Jing Han 1 2, Tianyi Zhang 4, Shangjin Li 4, Yanfei Hou 1, Huili Su 1, Fangping Han 1, Conggang Zhang 5 6
Abstract:
...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.
