title: Lung epithelial cells resist influenza A infection by inducing the expression of cytochrome c oxidase VIc which is modulated by miRNA 4276.
abstract: Influenza virus infection induces several changes in host miRNA profile, host cell death and tissue damage. Cytochrome c is a regulator of the intrinsic apoptotic pathway and is altered during viral infections. Within the first 3h of infection with influenza virus, significant down-regulation of hsa-miRNA-4276 (miRNA-4276) is followed by a 2-fold increase in cytochrome c oxidase VIC (COX6C) mRNA was found to occur in human alveolar and bronchial epithelial cells. Expression of caspase-9 also increased within the first 3h of infection, but subsequently decreased. Modulation of miR-4276 using mimic and inhibitor oligonucleotides showed significant down-regulation or up-regulation, respectively, of COX6C expression. Our data suggests that on initial exposure to influenza virus, host cells upregulate COX6C mRNA expression through silencing miR-4276 and repressed viral replication by inducing the apoptotic protein caspase-9. Taken together, these data suggest that miR-4276 may be an important regulator of the early stages of infection by influenza.
authors.affiliation: Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV, USA. Electronic address: seo8@cdc.gov.
authors.forename: Sreekumar
authors.initials: S
authors.lastname: Othumpangat
authors.affiliation: Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Noti
authors.affiliation: Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV, USA.
authors.forename: Donald H
authors.initials: DH
authors.lastname: Beezhold
mesh_terms: D000818:Animals; D001980:Bronchi / Q000166:cytology*; D002460:Cell Line; D004285:Dogs; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000276:immunology / Q000821:virology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000502:physiology; D053122:Influenza A Virus, H3N2 Subtype / Q000502:physiology*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D020545:Respiratory Mucosa / Q000166:cytology*
chemical_list: C404795:COX6c protein, human; C000595221:MIRN-4276 microRNA, human; D035683:MicroRNAs; D003576:Electron Transport Complex IV
keywords: COX6C; Influenza virus; Lung epithelial cells; miRNA