Single-Cell RNA Sequencing Transcriptomics Revealed HCMV IE2-Related Microglia Responses in Alzheimer’s-Like Disease in Transgenic Mice

Author:

Liu Fengjun,Wang Zhifei,Niu Delei,Zhang Xianjuan,Nan Fulong,Jiang Shasha,Li Jun,Yu Meng,Yang Xiaoli,Zhang Shuyun,Zhou Xiaoqiong,Wang Hui,Zhang Xueming,Liu Wenxuan,Li Zonghui,Wang Yunyang,Wang BinORCID

Abstract

Abstract    Although multiple factors are known to concur with Alzheimer’s disease (AD), the relationship between human cytomegalovirus (HCMV) and AD-like disease is unclear. Here, we propose a hypothesis that HCMV immediate-early 2 (IE2) protein promotes microglia activation and thus leads to AD-like disease. We successfully constructed IE2 transgenic mice expressing IE2 in the hippocampus. Single-cell sequencing analysis revealed that IE2 promoted the activation of microglia and upregulated the expression of disease-associated microglia genes. Differentially expressed gene analysis and pathway enrichment revealed that IE2 upregulated immune and nervous system disease-related genes. Immunohistochemical analysis showed that the expressions of both amyloid precursor protein (APP) and p-Tau were significantly upregulated in the brains of IE2 mice and were markers of AD. Taken together, these findings provide useful insights into AD-like disease activated by HCMV IE2.

Funder

Shandong Provincial Science and technology Foundation

Qingdao Municipal Science and technology Foundation

National Key Research and Development Program of China

Publisher

Springer Science and Business Media LLC

Subject

Neuroscience (miscellaneous),Cellular and Molecular Neuroscience,Neurology

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