title: Hepatitis A virus 3C protease cleaves NEMO to impair induction of beta interferon.
abstract: NEMO (NF-κB essential modulator) is a bridging adaptor indispensable for viral activation of interferon (IFN) antiviral response. Herein, we show that hepatitis A virus (HAV) 3C protease (3Cpro) cleaves NEMO at the Q304 residue, negating its signaling adaptor function and abrogating viral induction of IFN-β synthesis via the retinoic acid-inducible gene I/melanoma differentiation-associated protein 5 (RIG-I/MDA5) and Toll-like receptor 3 (TLR3) pathways. NEMO cleavage and IFN antagonism, however, were lost upon ablation of the catalytic activity of 3Cpro. These data describe a novel immune evasion mechanism of HAV.
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
authors.forename: Dang
authors.initials: D
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
authors.forename: Liurong
authors.initials: L
authors.lastname: Fang
authors.affiliation: Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
authors.forename: Dahai
authors.initials: D
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
authors.forename: Huanchun
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, Tennessee, USA kli1@uthsc.edu vet@mail.hzau.edu.cn.
authors.forename: Kui
authors.initials: K
authors.lastname: Li
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China kli1@uthsc.edu vet@mail.hzau.edu.cn.
authors.forename: Shaobo
authors.initials: S
authors.lastname: Xiao
mesh_terms: D000086042:3C Viral Proteases; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D030041:Hepatitis A virus / Q000201:enzymology*; D054884:Host-Pathogen Interactions; D006801:Humans; D006868:Hydrolysis; D051550:I-kappa B Kinase / Q000378:metabolism*; D057131:Immune Evasion; D016899:Interferon-beta / Q000037:antagonists & inhibitors*; D015398:Signal Transduction; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: C491731:IKBKG protein, human; D014764:Viral Proteins; D016899:Interferon-beta; D051550:I-kappa B Kinase; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases