title: Functional Analysis of Chicken IRF7 in Response to dsRNA Analog Poly(I:C) by Integrating Overexpression and Knockdown.
abstract: In order to develop novel strategies to protect against increasingly virulent bird-linked pathogens, a better understanding of the avian antiviral response mechanism is essential. Type I interferons (IFNs) are recognized as the first line of defense in a host's antiviral response; and it has been suggested that IRF7, a member of the IFN regulatory factor (IRF) family, plays an important role in modulating the immune response to avian influenza virus infection in chickens. The objective of this study was to identify candidate genes and pathways associated with IRF7 regulation at the transcriptome level as a first step towards elucidating the underlying cellular mechanisms of IRF7 modulation in the chicken antiviral response. IRF7 overexpression and knockdown DF-1 cell lines were established and stimulated by various pathogen-associated molecular patterns. Significant IRF7 and type I IFN expression changes were observed in both the IRF7 overexpression cell line and the IRF7 knockdown cell line upon exposure to the double stranded RNA (dsRNA) analog poly(I:C). Using RNA-seq based transcriptome analysis, we identified potential novel genes that IRF7 may help regulate as part of the host immune response to dsRNA; potential biomarkers and therapeutic targets revealed as a result of this study warrant further investigation. Based on our results, we suggest that IRF7 may have conserved functional activity in the avian antiviral response, and plays a crucial role in type I IFN regulation.
authors.affiliation: Integrative Genetics and Genomics Graduate Group, Department of Animal Science, University of California, Davis, California, United States of America.
authors.forename: Tae Hyun
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Integrative Genetics and Genomics Graduate Group, Department of Animal Science, University of California, Davis, California, United States of America.
authors.forename: Huaijun
authors.initials: H
authors.lastname: Zhou
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002645:Chickens / Q000235:genetics*; D003001:Cloning, Molecular; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D063990:Gene Ontology; D050839:Interferon Regulatory Factor-7 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D016898:Interferon-alpha / Q000235:genetics / Q000378:metabolism; D058977:Molecular Sequence Annotation; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics; D000069452:Pathogen-Associated Molecular Pattern Molecules / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology*; D012330:RNA, Double-Stranded / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D017423:Sequence Analysis, RNA
chemical_list: D050839:Interferon Regulatory Factor-7; D016898:Interferon-alpha; D000069452:Pathogen-Associated Molecular Pattern Molecules; D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering; D011070:Poly I-C