Abstract
Chikungunya virus (CHIKV) infection can cause severe arthralgia and chronic arthritis in humans. MicroRNAs (miRNA) have demonstrated their potential use as biomarker in variety of human pathologies and infections. This study was conducted to understand the miRNA signature in early CHIKV infection stages. In the current study, we used TaqMan-based quantitative PCR method to identify the miRNA signature of host response upon CHIKV infection in human and mouse fibroblast cells. The GO enrichment analysis suggests that the putative target genes of these differentially expressed miRNAs are to be involved in RIG-I pathway, TGF-beta-signaling pathway, JAK–STAT-signaling pathway, MAPK-signaling pathway, cytokine–cytokine receptor interactions, and Fc gamma R-mediated phagocytosis. The results obtained in the current study and earlier studies indicate the potential use of miR15, miR-16, miR-17, let-7e, miR-125, miR-99, and miR-23a as a biomarker in CHIKV infection. miRNAs such as miR-15a, miR-16, miR-140, miR-146a, miR-155, miR203, miR223, miR-499, and miR-363 which are implicated in rheumatoid arthritis showed differential regulation in CHIKV infection. The data obtained in this study provide valuable information on CHIKV-induced miRNA expression in mammalian fibroblast cells, and suggest that CHIKV may establish infection by regulating miRNA expression profile.
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Acknowledgements
The authors would like to acknowledge financial support provided by the Indian Council of Medical Research (ICMR), Ministry of Health and Family Welfare, Government of India. The funding agency had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Conceived and designed the experiments: DP and MSP. Performed the experiments: AM, PP, and SA. Analyzed the data: DP and MSP. Wrote the paper: DP and MSP.
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Supplementary Data SI1
: miRNA expression profiling data mouse fibroblast cells (Mocha): Mocha cells were infected with CHIKV and miRNA expression profiling was done at 2, 4, 8, and 16 h post-infection. The excel file sheets specifying miRNAs found to be more than twofold up-regulated or down-regulated (t test—P<0.05) at 2, 4, 8, and 16 h post-CHIKV infection as compared to control are shown along with the mean fold change values and standard deviation. (XLS 40 KB)
Supplementary Data SI2
: Biological functions of predicted target genes of differentially regulated miRNAs in mouse fibroblast cells. Mocha cells were infected with CHIKV and miRNA expression profiling was done at 2, 4, 8, and 16 h post-infection. The predicted target genes of miRNAs were placed in different biological processes based on analysis in the DAVID software. (XLS 191 KB)
Supplementary Data SI3
: Molecular processes of predicted target genes of differentially regulated miRNAs in mouse fibroblast cells. Mocha cells were infected with CHIKV and miRNA expression profiling was done at 2, 4, 8, and 16 h post-infection. The predicted target genes of miRNAs were placed in different molecular processes based on analysis in the DAVID software. (XLS 60 KB)
Supplementary Data SI4
: KEGG pathway of predicted target genes of differentially regulated miRNAs in mouse fibroblast cells. Mocha cells were infected with CHIKV and miRNA expression profiling was done at 2, 4, 8, and 16 h post-infection. The predicted target genes of miRNAs were placed in different KEGG pathways based on analysis in the DAVID software. (XLS 33 KB)
Supplementary Data SI5
: miRNA expression profiling data human fibroblast cells (1BR3): 1BR3 cells were infected with CHIKV and miRNA expression profiling was done at 2, 4, 8, and 16 h post-infection. The excel file sheets specifying miRNAs found to be more than twofold up-regulated or down-regulated (t test—P<0.05) at at 2, 4, 8, and 16 h post CHIKV infection as compared to control are shown along with the mean fold change values and standard deviation. (XLS 50 KB)
Supplementary Data SI6
: Biological functions of predicted target genes of differentially regulated miRNAs in human fibroblast cells. 1BR3 cells were infected with CHIKV and miRNA expression profiling was done at 2, 4, 8, and 16 h post-infection. The predicted target genes of miRNAs were placed in different biological processes based on analysis in the DAVID software. (XLS 613 KB)
Supplementary Data SI7
: Molecular processes of predicted target genes of differentially regulated miRNAs in human fibroblast cells. 1BR3 cells were infected with CHIKV and miRNA expression profiling was done at 2, 4, 8, and 16 h post-infection. The predicted target genes of miRNAs were placed in different molecular processes based on analysis in the DAVID software. (XLS 149 KB)
Supplementary Data SI8
: KEGG pathway of predicted target genes of differentially regulated miRNAs in human fibroblast cells. 1BR3 cells were infected with CHIKV and miRNA expression profiling was done at 2, 4, 8, and 16 h post-infection. The predicted target genes of miRNAs were placed in different KEGG pathways based on analysis in the DAVID software. (XLS 65 KB)
Supplementary Data SI9
: The miRNA signature in different cells after JE, DENV, WNV, and infection. (XLSX 15 KB)
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Parashar, D., Paingankar, M.S., More, A. et al. Altered microRNA expression signature in Chikungunya-infected mammalian fibroblast cells. Virus Genes 54, 502–513 (2018). https://doi.org/10.1007/s11262-018-1578-8
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DOI: https://doi.org/10.1007/s11262-018-1578-8