Single-cell immune landscape of the central nervous system of mice infected with rabies virus
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Updated: Aug 6, 2026
High-Resolution 3D Imaging of Rabies Virus Infection in Solvent-Cleared Brain Tissue
Published on: April 30, 2019
Xinyue Wang1,2,3,4,5,6,7, Xinjie Zhang2,8, Wenwen He2,3,4,5,6,7
1College of Wildlife and Protected Area, Northeast Forestry University, Harbin, China.
Background:
The fatality rate of virulent rabies virus (RABV) following central nervous system (CNS) invasion is nearly 100%. Infection with the virulent CVS-11 strain is associated with severe neurological symptoms and lethal outcomes, while the attenuated SRV9 strain can be cleared by the host. Although previous studies have investigated intracranial cytological and immunological changes, a high-resolution single-cell understanding is still lacking. Such resolution is essential for analyzing immune cell heterogeneity and intercellular communication networks.
Objectives:
This study aimed to depict the immune response after CVS-11 and SRV9 infections at single-cell resolution, addressing the immune mechanisms influencing RABV infection outcomes.
Methods:
We performed single-cell RNA sequencing (scRNA-seq) on brains from CVS-11 infected, SRV9 infected, and mock infected mice. By analyzing over 100,000 cells, we constructed a comprehensive atlas of CNS immune responses.
Result:
Compared with SRV9 infection, CVS-11 infection was associated with transcriptional signatures indicative of: a trend of microglial shifting toward a phagocytic signature enriched phagocytic phenotype, elevated expression of genes related to excessive neutrophilic inflammation, down regulation of NK cell functional genes (suggesting potential dysfunction), and increased expression of T cell exhaustion-related genes. In contrast, SRV9 infection correlated with microglial features indicative of an immunoregulatory phenotype, more precise NK cell antiviral function, more complete T cell activation and memory formation, and more coordinated immune interactions.
Conclusion:
The scRNA-seq data from this study suggest that virulent and attenuated RABV strains may induce distinct patterns of immune responses in the central nervous system: the former is accompanied by features of dysfunctional cellular responses, whereas the latter presents protective immune features associated with viral clearance. Notably, a set of signature genes (Fkbp5, Apod, Klf2, Socs3) and pathways was identified associated with lethal RABV infection. These findings provide new insights for rabies vaccine design and immunotherapy.
