title: microRNAs in circulation are altered in response to influenza A virus infection in humans.
abstract: Changes in microRNA expression have been detected in vitro in influenza infected cells, yet little is known about them in patients. microRNA profiling was performed on whole blood of H1N1 patients to identify signature microRNAs to better understand the gene regulation involved and possibly improve diagnosis. Total RNA extracted from blood samples of influenza infected patients and healthy controls were subjected to microRNA microarray. Expression profiles of circulating microRNAs were altered and distinctly different in influenza patients. Expression of highly dysregulated microRNAs were validated using quantitative PCR. Fourteen highly dysregulated miRNAs, identified from the blood of influenza infected patients, provided a clear distinction between infected and healthy individuals. Of these, expression of miR-1260, -26a, -335*, -576-3p, -628-3p and -664 were consistently dysregulated in both whole blood and H1N1 infected cells. Potential host and viral gene targets were identified and the impact of microRNA dysregulation on the host proteome was studied. Consequences of their altered expression were extrapolated to changes in the host proteome expression. These highly dysregulated microRNAs may have crucial roles in influenza pathogenesis and are potential biomarkers of influenza.
authors.affiliation: Department of Medicine, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore, Singapore.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Tambyah
authors.forename: Sugunavathi
authors.initials: S
authors.lastname: Sepramaniam
authors.forename: Jaminah
authors.initials: J
authors.lastname: Mohamed Ali
authors.forename: Siaw Ching
authors.initials: SC
authors.lastname: Chai
authors.forename: Priyadharshini
authors.initials: P
authors.lastname: Swaminathan
authors.forename: Arunmozhiarasi
authors.initials: A
authors.lastname: Armugam
authors.forename: Kandiah
authors.initials: K
authors.lastname: Jeyaseelan
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D002460:Cell Line; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000502:physiology*; D007251:Influenza, Human / Q000175:diagnosis / Q000235:genetics* / Q000821:virology*; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020543:Proteome / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D059467:Transcriptome
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; D020543:Proteome; C582445:MIRN1260 microRNA, human; C528163:MIRN26 microRNA, human; C556347:MIRN335 microRNA, human; C000590114:MIRN576 microRNA, human; C000589022:MIRN628 microRNA, human; C000590115:MIRN664 microRNA, human