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Infection with street strain rabies virus induces modulation of the microRNA profile of the mouse brain

Pingsen Zhao12, Lili Zhao23, Kun Zhang12, Hao Feng23, Hualei Wang2, Tiecheng Wang2, Tao Xu4, Na Feng2, Chengyu Wang2, Yuwei Gao2, Geng Huang2, Chuan Qin1, Songtao Yang2* and Xianzhu Xia12*

Author Affiliations

1 Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100021, China

2 Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, 130122, China

3 College of Animal Science and Veterinary Medicine, Jilin University, Changchun, 130062, China

4 Medical College of Soochow University, Suzhou, 215123, China

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Virology Journal 2012, 9:159  doi:10.1186/1743-422X-9-159

Published: 11 August 2012

Abstract

Background

Rabies virus (RABV) causes a fatal infection of the central nervous systems (CNS) of warm-blooded animals. Once the clinical symptoms develop, rabies is almost invariably fatal. The mechanism of RABV pathogenesis remains poorly understood. Recent studies have shown that microRNA (miRNA) plays an important role in the pathogenesis of viral infections. Our recent findings have revealed that infection with laboratory-fixed rabies virus strain can induce modulation of the microRNA profile of mouse brains. However, no previous report has evaluated the miRNA expression profile of mouse brains infected with RABV street strain.

Results

The results of microarray analysis show that miRNA expression becomes modulated in the brains of mice infected with street RABV. Quantitative real-time PCR assay of the differentially expressed miRNAs confirmed the results of microarray assay. Functional analysis showed the differentially expressed miRNAs to be involved in many immune-related signaling pathways, such as the Jak-STAT signaling pathway, the MAPK signaling pathway, cytokine-cytokine receptor interactions, and Fc gamma R-mediated phagocytosis. The predicted expression levels of the target genes of these modulated miRNAs were found to be correlated with gene expression as measured by DNA microarray and qRT-PCR.

Conclusion

RABV causes significant changes in the miRNA expression profiles of infected mouse brains. Predicted target genes of the differentially expression miRNAs are associated with host immune response, which may provide important information for investigation of RABV pathogenesis and therapeutic method.

Keywords:
Street strain rabies virus; Brain infection; MicroRNA profiling; Gene profiling; Target prediction; Functional enrichment