title: miR-144 attenuates the host response to influenza virus by targeting the TRAF6-IRF7 signaling axis.
abstract: Antiviral responses must rapidly defend against infection while minimizing inflammatory damage, but the mechanisms that regulate the magnitude of response within an infected cell are not well understood. miRNAs are small non-coding RNAs that suppress protein levels by binding target sequences on their cognate mRNA. Here, we identify miR-144 as a negative regulator of the host antiviral response. Ectopic expression of miR-144 resulted in increased replication of three RNA viruses in primary mouse lung epithelial cells: influenza virus, EMCV, and VSV. We identified the transcriptional network regulated by miR-144 and demonstrate that miR-144 post-transcriptionally suppresses TRAF6 levels. In vivo ablation of miR-144 reduced influenza virus replication in the lung and disease severity. These data suggest that miR-144 reduces the antiviral response by attenuating the TRAF6-IRF7 pathway to alter the cellular antiviral transcriptional landscape.
authors.affiliation: Center for Infectious Disease Research, Seattle, WA United States of America.
authors.forename: Carrie M
authors.initials: CM
authors.lastname: Rosenberger
authors.affiliation: Center for Infectious Disease Research, Seattle, WA United States of America.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Podyminogin
authors.affiliation: Center for Infectious Disease Research, Seattle, WA United States of America.
authors.forename: Alan H
authors.initials: AH
authors.lastname: Diercks
authors.affiliation: Department of Comparative Medicine, School of Medicine, University of Washington, Seattle, WA, United States of America.
authors.forename: Piper M
authors.initials: PM
authors.lastname: Treuting
authors.affiliation: Center for Infectious Disease Research, Seattle, WA United States of America.
authors.forename: Jacques J
authors.initials: JJ
authors.lastname: Peschon
authors.affiliation: Center for Infectious Disease Research, Seattle, WA United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Rodriguez
authors.affiliation: Institute for Systems Biology, Seattle, WA, United States of America.
authors.forename: Madhumati
authors.initials: M
authors.lastname: Gundapuneni
authors.affiliation: Hematology, St. Jude Children's Research Hospital, Memphis, TN United States of America.
authors.forename: Mitchell J
authors.initials: MJ
authors.lastname: Weiss
authors.affiliation: Center for Infectious Disease Research, Seattle, WA United States of America.
authors.forename: Alan
authors.initials: A
authors.lastname: Aderem
mesh_terms: D000818:Animals; D002460:Cell Line; D004847:Epithelial Cells / Q000821:virology; D020869:Gene Expression Profiling; D017930:Genes, Reporter; D006801:Humans; D007251:Influenza, Human / Q000276:immunology* / Q000821:virology; D008168:Lung / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009975:Orthomyxoviridae / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D048029:TNF Receptor-Associated Factor 6 / Q000235:genetics* / Q000378:metabolism; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D019562:Viral Load; D014779:Virus Replication
chemical_list: C551064:MIRN144 microRNA, mouse; D035683:MicroRNAs; D012333:RNA, Messenger; D048029:TNF Receptor-Associated Factor 6; C486461:Traf7 protein, mouse; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins