tetano
Editor, Senior Moderator
J Gen Virol. 2013 Jan 23. [Epub ahead of print]
Host microRNA molecular signatures associated with human H1N1 and H3N2 influenza A viruses reveal an unanticipated antiviral activity for miR-146a.
Terrier O, Textoris J, Carron C, Marcel V, Bourdon JC, Rosa-Calatrava M.
Source
Universite Claude Bernard Lyon 1;
Abstract
While post-transcriptional regulation of gene expression by miRNAs have been shown to be involved in influenza virus replication cycle, only a few studies have further investigated this aspect in a human cellular model infected with human influenza viruses. In this study, we performed miRNA global profiling in human lung epithelial cells (A549) infected by two different subtypes of human influenza A viruses (H1N1 and H3N2). We identified a common miRNA signature in response to infection by the two different strains, highlighting a pool of five miRNAs commonly deregulated, which are known to be involved in the innate immune response or apoptosis. Among the five miRNA hits, the only up-regulated miRNA in response to influenza infection corresponded to miR-146a. Based on a previously published gene expression dataset, we extracted inversely correlated miR-146a target genes and determined their first-level interactants. This functional analysis revealed 8 distinct biological processes strongly associated with these interactants: TLR pathway, innate immune response, cytokine production and apoptosis. To better understand the biological significance of miR-146a up-regulation, using a reporter assay and a specific anti-miR-146a inhibitor, we confirmed that infection increases the endogenous miR-146a promoter activity and that inhibition of miR-146a significantly increased viral propagation. Altogether, our results suggest a functional role of miR-146a in the outcome of influenza infection, at the crossroads of several biological processes.
PMID:
23343627
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23343627
Host microRNA molecular signatures associated with human H1N1 and H3N2 influenza A viruses reveal an unanticipated antiviral activity for miR-146a.
Terrier O, Textoris J, Carron C, Marcel V, Bourdon JC, Rosa-Calatrava M.
Source
Universite Claude Bernard Lyon 1;
Abstract
While post-transcriptional regulation of gene expression by miRNAs have been shown to be involved in influenza virus replication cycle, only a few studies have further investigated this aspect in a human cellular model infected with human influenza viruses. In this study, we performed miRNA global profiling in human lung epithelial cells (A549) infected by two different subtypes of human influenza A viruses (H1N1 and H3N2). We identified a common miRNA signature in response to infection by the two different strains, highlighting a pool of five miRNAs commonly deregulated, which are known to be involved in the innate immune response or apoptosis. Among the five miRNA hits, the only up-regulated miRNA in response to influenza infection corresponded to miR-146a. Based on a previously published gene expression dataset, we extracted inversely correlated miR-146a target genes and determined their first-level interactants. This functional analysis revealed 8 distinct biological processes strongly associated with these interactants: TLR pathway, innate immune response, cytokine production and apoptosis. To better understand the biological significance of miR-146a up-regulation, using a reporter assay and a specific anti-miR-146a inhibitor, we confirmed that infection increases the endogenous miR-146a promoter activity and that inhibition of miR-146a significantly increased viral propagation. Altogether, our results suggest a functional role of miR-146a in the outcome of influenza infection, at the crossroads of several biological processes.
PMID:
23343627
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23343627