title: Rotavirus nonstructural protein 1 antagonizes innate immune response by interacting with retinoic acid inducible gene I.
abstract: BACKGROUND
  The nonstructural protein 1 (NSP1) of rotavirus has been reported to block interferon (IFN) signaling by mediating proteasome-dependent degradation of IFN-regulatory factors (IRFs) and (or) the β-transducin repeat containing protein (β-TrCP). However, in addition to these targets, NSP1 may subvert innate immune responses via other mechanisms.
  
  
  RESULTS
  The NSP1 of rotavirus OSU strain as well as the IRF3 binding domain truncated NSP1 of rotavirus SA11 strain are unable to degrade IRFs, but can still inhibit host IFN response, indicating that NSP1 may target alternative host factor(s) other than IRFs. Overexpression of NSP1 can block IFN-β promoter activation induced by the retinoic acid inducible gene I (RIG-I), but does not inhibit IFN-β activation induced by the mitochondrial antiviral-signaling protein (MAVS), indicating that NSP1 may target RIG-I. Immunoprecipitation experiments show that NSP1 interacts with RIG-I independent of IRF3 binding domain. In addition, NSP1 induces down-regulation of RIG-I in a proteasome-independent way.
  
  
  CONCLUSIONS
  Our findings demonstrate that inhibition of RIG-I mediated type I IFN responses by NSP1 may contribute to the immune evasion of rotavirus.
authors.affiliation: State Key Laboratory of Molecular Virology and Genetic Engineering, Institute of Pathogen Biology, Peking Union Medical College & Chinese Academy of Medical Sciences, # 9 Dong Dan San Tiao, Dongcheng District, Beijing 100730, PR China.
authors.forename: Lan
authors.initials: L
authors.lastname: Qin
authors.forename: Lili
authors.initials: L
authors.lastname: Ren
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Zhou
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Lei
authors.forename: Lan
authors.initials: L
authors.lastname: Chen
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Xue
authors.forename: Xinlei
authors.initials: X
authors.lastname: Liu
authors.forename: Jianwei
authors.initials: J
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Hung
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D057131:Immune Evasion; D007113:Immunity, Innate; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016899:Interferon-beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012401:Rotavirus / Q000276:immunology*; D012400:Rotavirus Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D044844:beta-Transducin Repeat-Containing Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D050835:Interferon Regulatory Factors; C505371:MAVS protein, human; C431552:RAI1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D017361:Viral Nonstructural Proteins; D044844:beta-Transducin Repeat-Containing Proteins; C104282:nsp1 protein, Rotavirus; D016899:Interferon-beta; D046988:Proteasome Endopeptidase Complex