Wang Dang, Fang Liurong, Wei Dahai, Zhang Huan, Luo Rui, Chen Huanchun, Li Kui, Xiao Shaobo
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
J Virol. 2014 Sep 1;88(17):10252-8. doi: 10.1128/JVI.00869-14. Epub 2014 Jun 11.
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.
NEMO(核因子κB关键调节因子)是一种衔接适配蛋白,对于病毒激活干扰素(IFN)抗病毒反应不可或缺。在此,我们表明甲型肝炎病毒(HAV)3C蛋白酶(3Cpro)在Q304残基处切割NEMO,使其信号转导适配功能丧失,并通过视黄酸诱导基因I/黑色素瘤分化相关蛋白5(RIG-I/MDA5)和Toll样受体3(TLR3)途径消除病毒诱导的IFN-β合成。然而,3Cpro催化活性缺失后,NEMO切割和IFN拮抗作用消失。这些数据描述了一种新型的HAV免疫逃逸机制。