The Npro product of classical swine fever virus interacts with IκBα, the NF-κB inhibitor
The Npro product of classical swine fever virus interacts with IκBα, the NF-κB inhibitor
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DOI：
10.1099/vir.0.83643-0
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发表时间：
2008-08-01
影响因子：
3.8
通讯作者：
Seago, Julian
中科院分区：
文献类型：
--
作者：
Doceul, Virginie;Charleston, Bryan;Seago, Julian
猪瘟病毒（CSFV）属于鼠疫病毒属，是猪瘟（猪的一种出血性疾病）的病原体。该病毒在宿主细胞中复制而不激活干扰素（IFN）的产生，并且据报道是双链rna诱导的细胞凋亡的拮抗剂。猪瘟病毒的N端蛋白酶（N pro）负责逃避宿主先天免疫反应。为了鉴定与CSFV N pro产物相互作用的细胞蛋白，我们对人类文库进行酵母双杂交筛选，鉴定出nf - i13的抑制剂li Bj， nf - i13是一种参与细胞凋亡、免疫应答和IFN产生控制的转录因子。IN pro_, i 13)，。通过酵母双杂交分析和额外的共沉淀试验证实了相互作用。结果还表明，在稳定转染的细胞和猪瘟病毒感染的细胞中，N pro定位于细胞质和核室。在肿瘤坏死因子α的刺激下，表达Nor'的pk - 15细胞系表现出短暂的核积累pli，713j。CSFV感染对乙型肝炎无明显影响。观察到Nl ' -/ B p65的定位或激活。
Classical swine fever virus (CSFV) belongs to the genus Pestivirus and is the causative agent of classical swine fever, a haemorrhagic disease of pigs. The virus replicates in host cells without activating interferon (IFN) production and has been reported to be an antagonist of doublestranded RNA-induced apoptosis. The N-terminal protease (N pro) of CSFV is responsible for this evasion of the host innate immune response. In order to identify cellular proteins that interact with the N pro product of CSFV, a yeast two-hybrid screen of a human library was carried out, which identified li Bj,, the inhibitor of NF-i 13, a transcription factor involved in the control of apoptosis, the immune response and IFN production. The IN pro_, i 13),. interaction was confirmed using yeast two-hybrid analysis and additional co-precipitation assays. It was also shown that N pro localizes to both the cytoplasmic and nuclear compartments in stably transfected cells and in CSFVinfected cells. Following stimulation by tumour necrosis factor alpha, PK-1 5 cell lines expressing Nor' exhibited transient nuclear accumulation of pli,713j., but no effect of CSFV infection on li B:t. localization or Nl`-/ B p65 activation was observed.