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Published on: December 3, 2019
MicroRNA transcriptome profiling of mice brains infected with Japanese encephalitis virus by RNA sequencing
Xin-Feng Li1, Rui-Bing Cao1, Jun Luo2
1College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China.
Abstract:
Japanese encephalitis (JE) is a mosquito borne viral disease, caused by Japanese encephalitis virus (JEV) infection producing severe neuroinflammation in the central nervous system (CNS) with the associated disruption of the blood brain barrier. MicroRNAs (miRNAs) are a family of 21-24 nt small non-coding RNAs that play important post-transcriptional regulatory roles in gene expression and have critical roles in virus pathogenesis. We examined the potential roles of miRNAs in JEV-infected suckling mice brains and found that JEV infection changed miRNA expression profiles when the suckling mice began showing nervous symptoms. A total of 1062 known and 71 novel miRNAs were detected in JEV-infected group, accompanied with 1088 known and 75 novel miRNAs in mock controls. Among these miRNAs, one novel and 25 known miRNAs were significantly differentially expressed, including 18 up-regulated and 8 down-regulated miRNAs which were further confirmed by real-time PCR. Gene ontology (GO) and signaling pathway analysis of the predicted target mRNAs of the modulated miRNAs showed that they are correlated with the regulation of apoptosis, neuron differentiation, antiviral immunity and infiltration of mouse brain, and the validated targets of 12 differentially expressed miRNAs were enriched for the regulation of cell programmed death, proliferation, transcription, muscle organ development, erythrocyte differentiation, gene expression, plasma membrane and protein domain specific binding. KEGG analysis further reveals that the validated target genes were involved in the Pathways in cancer, Neurotrophin signaling pathway, Toll like receptor signaling pathway, Endometrial cancer and Jak-STAT signaling pathway. We constructed the interaction networks of miRNAs and their target genes according to GO terms and KEGG pathways and the expression levels of several target genes were examined. Our data provides a valuable basis for further studies on the regulatory roles of miRNAs in JE pathogenesis.
Insights
Japanese encephalitis virus (JEV) infection alters microRNA (miRNA) expression in mouse brains, impacting neuroinflammation and pathogenesis. These findings reveal key miRNA roles in central nervous system responses to JEV.
Area of Science:
- Neuroscience
- Virology
- Molecular Biology
Background:
- Japanese encephalitis (JE) is a severe mosquito-borne viral disease causing neuroinflammation.
- MicroRNAs (miRNAs) are small non-coding RNAs critical in gene regulation and viral pathogenesis.
Purpose of the Study:
- To investigate the role of miRNAs in Japanese encephalitis virus (JEV)-infected mouse brains.
- To identify differentially expressed miRNAs and their target genes during JEV infection.
Main Methods:
- Analysis of miRNA expression profiles in JEV-infected and control suckling mice.
- Validation of differentially expressed miRNAs using real-time PCR.
- Bioinformatic analysis (GO, KEGG) of predicted and validated miRNA targets.
Main Results:
- JEV infection significantly altered miRNA expression profiles in mouse brains.
- 18 up-regulated and 8 down-regulated miRNAs were identified and validated.
- Target gene analysis indicated involvement in apoptosis, neuroinflammation, and immune signaling pathways.
Conclusions:
- MicroRNAs play a significant role in the pathogenesis of Japanese encephalitis.
- Modulated miRNAs and their targets offer potential insights into JE disease mechanisms.
- This study provides a foundation for further research into miRNA-mediated regulation in JE.
