Combined miRNA and mRNA signature identifies key molecular players and pathways involved in chikungunya virus infection in human cells
Autor(es): Saxena Tanvi, Tandon Bhavna, Sharma Shivani, Chameettachal Shibu, Ray Pratima, Ray Alok R, Kulshreshtha Ritu
Resumo: Since its discovery, Chikungunya fever caused by a virus (CHIKV) has ravaged most of Africa - Southeast Asia. Despite there being more than a million reported cases in India alone - the seriousness of the disease in the chronic phase, a clear underst-ing of the disease pathogenesis - host response remains elusive. Here, we use microarray technology - quantitative PCR method to establish the complete miRNA, snoRNA - mRNA signature of host response upon CHIKV infection in human cell line infection model, HEK293T. The results were further validated in human primary cells (dermal fibroblasts). miRNA expression profiling revealed regulation of 152 miRNAs post CHIKV infection. An interesting overlap in miRNA signature was seen majorly with HCV, HPV - HIV1 virus. The microarray data further validated by qRT-PCR revealed induction of miR-744, miR-638, miR-503 - others among the top upregulated miRNAs. Notably, we found induction of snoRNAs belonging to C/D cluster including close paralogs of U3, U44, U76 - U78 snoRNAs. Genes were found to be differentially expressed along 3 major pathways; TGF-?, endocytosis - the cell cycle pathways. qRT-PCR data confirmed strong induction of TGF-? (SMAD6, JUN, SKIL) - endocytosis pathway (CXCR4, HSPA8, ADRB1) genes while downregulation of cell cycle genes (CDC27 - CDC23). Interestingly, use of TGF-? inhibitor, SB-431542, increased CHIKV mediated cell death. Overall, this study aims at providing the first complete transcriptome signature of host response upon CHIKV infection to aid identification of possible biomarkers - therapeutic targets.
Imprenta: PloS One, v. 8, n. 11, p. e79886, 2013
Identificador do objeto digital: 10.1371/journal.pone.0079886
Descritores: Chikungunya virus - Cell ; Chikungunya virus - Pathogenesis ; Chikungunya virus - RNA ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Chikungunya fever
Data de publicação: 2013
