RESUMEN
Chandipura virus (CHPV) is a neurotropic virus, known to cause encephalitis in humans. The microRNAs (miRNA/miR) play an important role in the pathogenesis of viral infection. The present study is focused on the role of miRNAs during CHPV (strain 1653514) infection in human microglial cells. The deep sequencing of CHPV-infected human microglial cells identified a total of 12 differentially expressed miRNA (DEMs). To elucidate the role of DEMs, the target gene prediction, Gene Ontology term (GO Term), pathway enrichment analysis, and miRNA-messenger RNA (mRNA) interaction network analysis was performed. The GO terms and pathway enrichment analysis provided 146 enriched genes; which were involved in interferon response, cytokine and chemokine signaling. Further, the WGCNA (weighted gene coexpression network analysis) of the enriched genes were discretely categorized into three modules (blue, brown, and turquoise). The hub genes in the blue module may correlate to CHPV induced neuroinflammation. Altogether, the miRNA-mRNA interaction network and WGCNA study revealed the following pairs, hsa-miR-542-3p and FAF1, hsa-miR-92a-1-5p and MYD88, and hsa-miR-3187-3p and TNFRSF21, which may contribute to neuroinflammation during CHPV infection in human microglial cells.
Asunto(s)
Redes Reguladoras de Genes/genética , MicroARNs/genética , Microglía/metabolismo , Vesiculovirus/fisiología , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Reguladoras de la Apoptosis/genética , Humanos , MicroARNs/metabolismo , Factor 88 de Diferenciación Mieloide/genética , Enfermedades Neuroinflamatorias/genética , Enfermedades Neuroinflamatorias/virología , Receptores del Factor de Necrosis Tumoral/genética , Infecciones por Rhabdoviridae/genética , Infecciones por Rhabdoviridae/virologíaRESUMEN
Chikungunya virus (CHIKV) is an alphavirus transmitted by mosquitoes. CHIKV infection leads to polyarthritis and polyarthralgia among patients. The synovial fibroblasts are the primary target for CHIKV. The microRNAs (miRNAs) are the small endogenous noncoding RNAs which posttranscriptionally regulate the expression of genes by binding to their target messenger RNAs (mRNAs) through their 3'-untranslated regions. The miRNAs are the key regulators for various pathological processes including viral infection, cancer, cardiovascular disease, and neurodegeneration. This study was designed to dissect out the roles of miRNAs during CHIKV (Ross Strain E1: A226V) infection in primary human synovial fibroblasts. The miRNA microarray profiling was performed on the primary human synovial fibroblasts infected by CHIKV. The gene target prediction analysis, enrichment, and network analysis were performed by various bioinformatics analyses. The subset of 26 differentially expressed microRNAs (DEMs) were identified through microarray profiling and were further screened for gene predictions, Gene Ontology, pathway enrichment, and miRNA-mRNA network using various bioinformatics tools. The bioinformatics analysis indicates the role of DEMs by suppressing the immune response which may contribute to CHIKV persistence in human primary synovial fibroblasts. Our study provides the plausible roles of DEMs, miRNAs, and mRNA interactions and pathways involved in the molecular pathogenesis of CHIKV.