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Updated: Aug 10, 2026
Isolation of Region-specific Microglia from One Adult Mouse Brain Hemisphere for Deep Single-cell RNA Sequencing
Published on: December 3, 2019
Single-Cell RNA Sequencing Transcriptomics Revealed HCMV IE2-Related Microglia Responses in Alzheimer's-Like Disease
Fengjun Liu1, Zhifei Wang2, Delei Niu3
1Department of Special Medicine, School of Basic Medicine, Qingdao University, Qingdao, 266000, China.
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.
Insights
Human cytomegalovirus (HCMV) IE2 protein may drive Alzheimer's disease (AD) by activating microglia. This study found IE2 protein upregulated AD markers in mouse brains, suggesting a potential link.
Area of Science:
- Neuroscience
- Virology
- Immunology
Background:
- Alzheimer's disease (AD) pathogenesis involves multiple factors, but the role of human cytomegalovirus (HCMV) remains unclear.
- HCMV is a common virus, and understanding its potential contribution to neurodegenerative diseases like AD is crucial.
Purpose of the Study:
- To investigate the hypothesis that HCMV immediate-early 2 (IE2) protein promotes microglia activation, potentially leading to AD-like pathology.
- To explore the molecular mechanisms linking HCMV IE2 to neuroinflammation and AD markers.
Main Methods:
- Construction of IE2 transgenic mice expressing the HCMV IE2 protein in the hippocampus.
- Single-cell sequencing to analyze microglia activation and gene expression.
- Differential gene expression and pathway enrichment analysis.
- Immunohistochemical analysis to detect AD biomarkers (APP and p-Tau).
Main Results:
- IE2 expression in mice led to significant microglia activation and upregulation of disease-associated microglia genes.
- IE2 upregulated genes related to immune and nervous system diseases.
- Significant upregulation of amyloid precursor protein (APP) and phosphorylated tau (p-Tau) was observed in the brains of IE2 mice.
Conclusions:
- HCMV IE2 protein can promote microglia activation and upregulate key Alzheimer's disease markers (APP and p-Tau).
- These findings suggest a potential causal role for HCMV IE2 in the development of AD-like pathology.
- This research offers insights into the interplay between viral infections and neurodegeneration.
