Department of Special Medicine, School of Basic Medicine, Qingdao University, Qingdao, 266000, China.
Clinical Laboratory, Qingdao Women and Children's Hospital of Qingdao University, Shandong, Qingdao, 266000, China.
Mol Neurobiol. 2024 Mar;61(3):1331-1345. doi: 10.1007/s12035-023-03553-y. Epub 2023 Sep 13.
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.
虽然已知多种因素与阿尔茨海默病（AD）有关，但人巨细胞病毒（HCMV）与 AD 样疾病之间的关系尚不清楚。在这里，我们提出一个假设，即 HCMV 立即早期 2（IE2）蛋白促进小胶质细胞激活，从而导致 AD 样疾病。我们成功构建了在海马区表达 IE2 的 IE2 转基因小鼠。单细胞测序分析显示，IE2 促进了小胶质细胞的激活，并上调了与疾病相关的小胶质细胞基因的表达。差异表达基因分析和通路富集分析显示，IE2 上调了免疫和神经系统疾病相关基因。免疫组织化学分析显示，IE2 小鼠大脑中淀粉样前体蛋白（APP）和 p-Tau 的表达均显著上调，这是 AD 的标志物。综上所述，这些发现为 HCMV IE2 激活的 AD 样疾病提供了有用的见解。
