title: NRAV, a long noncoding RNA, modulates antiviral responses through suppression of interferon-stimulated gene transcription.
abstract: Long noncoding RNAs (lncRNAs) modulate various biological processes, but their role in host antiviral responses is largely unknown. Here we identify a lncRNA as a key regulator of antiviral innate immunity. Following from the observation that a lncRNA that we call negative regulator of antiviral response (NRAV) was dramatically downregulated during infection with several viruses, we ectopically expressed NRAV in human cells or transgenic mice and found that it significantly promotes influenza A virus (IAV) replication and virulence. Conversely, silencing NRAV suppressed IAV replication and virus production, suggesting that reduction of NRAV is part of the host antiviral innate immune response to virus infection. NRAV negatively regulates the initial transcription of multiple critical interferon-stimulated genes (ISGs), including IFITM3 and MxA, by affecting histone modification of these genes. Our results provide evidence for a lncRNA in modulating the antiviral interferon response.
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ouyang
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; School of Life Sciences, Anhui University, Hefei 230601, China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Zhu
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yuhai
authors.initials: Y
authors.lastname: Chen
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Wei
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China.
authors.forename: Qinghuang
authors.initials: Q
authors.lastname: Chen
authors.affiliation: College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Chi
authors.affiliation: College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China.
authors.forename: Baomin
authors.initials: B
authors.lastname: Qi
authors.affiliation: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences & Comparative Medical Center, Beijing 100021, China.
authors.forename: Lianfeng
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Intelligent Information Processing, Institute of Computing Technology, Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: George Fu
authors.initials: GF
authors.lastname: Gao
authors.affiliation: Gene Therapy Program, Departments of Microbiology and Immunology, Medicine and Genetics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
authors.forename: Guoshun
authors.initials: G
authors.lastname: Wang
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China. Electronic address: chenjl@im.ac.cn.
authors.forename: Ji-Long
authors.initials: JL
authors.lastname: Chen
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015536:Down-Regulation; D020868:Gene Silencing; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D009980:Influenza A virus / Q000472:pathogenicity* / Q000502:physiology; D007372:Interferons / Q000276:immunology*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D046228:Microarray Analysis; D008969:Molecular Sequence Data; D064547:Myxovirus Resistance Proteins / Q000378:metabolism; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding / Q000235:genetics*; D014158:Transcription, Genetic; D014779:Virus Replication
chemical_list: D008565:Membrane Proteins; D064547:Myxovirus Resistance Proteins; D062085:RNA, Long Noncoding; C462181:fragilis protein, mouse; D007372:Interferons