Co-expression analysis suggests lncRNA-mRNA interactions enhance antiviral immune response during acute Chikungunya fever in whole blood of pediatric patients

Abstract

Chikungunya virus is an arbovirus that causes the neglected tropical disease chikungunya fever, common in tropical areas worldwide. There is evidence that arboviruses alter host transcriptome and modulate immune response; this modulation may involve transcriptional and post-transcriptional control mechanisms mediated by long non-coding RNAs (lncRNAs). Herein, we employed bioinformatic analysis to evaluate co-expression of lncRNAs and their putative target mRNAs in whole blood during natural Chikungunya infection in adolescent boys. Sequencing data from GSE99992 was uploaded to the Galaxy web server, where data was aligned with HISAT2, gene counts were estimated with HTSeq-count, and differential expression was run with DESeq2. After gene classification with Biomart, Pearson’s correlation was applied to identify potential interactions between lncRNAs and mRNAs, which were later classified into cis and trans according to genomic location (FEELnc) and binding potential (LncTar), respectively. We identified 1,975 mRNAs and 793 lncRNAs that were differentially expressed between the acute and convalescent stages of infection in the blood. Of the co-expressed lncRNAs and mRNAs, 357 potentially interact in trans and 9 in cis; their target mRNAs enriched pathways related to immune response and viral infections. Out of 52 enriched KEGG pathways, the RIG-I like receptor signaling is enriched by the highest number of target mRNAs. This pathway starts with the recognition of viral pathogens, leading to innate immune response mediated by the production of IFN-I and inflammatory cytokines. Our findings indicate that alterations in lncRNA expression in adolescent boys, induced by acute Chikungunya infection, potentially modulate mRNAs that contribute to antiviral immune responses.

Toward a Categorization of Virus-ncRNA Interactions in the World of RNA to Disentangle the Tiny Secrets of Dengue Virus

“…Novel data to uncover the role of miRNAs in host defense against Hepatitis C virus (HCV) and Ebola virus (EBV) infections reveal that liver-specific microRNA-122 (miR-122) stimulates HCV internal ribosome entry site (IRES)-dependent translation due to RNA-RNA interactions, as well as host miRNA expression [66][67][68]. It was recently suggested, via a coexpression analysis, that lncRNA-mRNA interactions enhance the antiviral immune response during acute chikungunya fever in the whole blood of pediatric patients [69].…”

The relationship of peripheral blood lncRNA-PVT1 and miR-146a levels with Th17/Treg cytokines in patients with Hashimoto’s thyroiditis and their clinical significance

“…Long noncoding RNAs (lncRNAs) refers to a specific class of RNA molecules greater than 200 base pairs in length that are cell-and tissue-specific [7]. LncRNAs play a prominent role in immune cell differentiation, proliferation, and apoptosis through the modulation of target gene expression, and are essential for regulating immune responses and maintaining immune balance [8,9,10]. The lncRNA-plasmacytoma variant translocation 1 (PVT1) is situated at 8q24.…”