Varicella-Zoster Virus Infection Triggers Formation of an Interleukin-1β (IL-1β)-processing Inflammasome Complex

被引:76
作者
Nour, Adel M. [1 ,2 ]
Reichelt, Mike [1 ,2 ]
Ku, Chia-Chi [4 ]
Ho, Min-Yin [4 ]
Heineman, Thomas C. [3 ]
Arvin, Ann M. [1 ,2 ]
机构
[1] Stanford Univ, Dept Pediat, Sch Med, Stanford, CA 94305 USA
[2] Stanford Univ, Dept Microbiol & Immunol, Sch Med, Stanford, CA 94305 USA
[3] GlaxoSmithKline Biol, King Of Prussia, PA 19101 USA
[4] Natl Taiwan Univ, Coll Med, Grad Inst Immunol, Taipei 10764, Taiwan
基金
美国国家卫生研究院;
关键词
GLOMERULAR MESANGIAL CELLS; INNATE IMMUNE-RESPONSE; NALP3; INFLAMMASOME; AIM2; MONONUCLEAR-CELLS; CASPASE-1; ACTIVATION; MURINE MACROPHAGES; NLRP3; VIRAL REPLICATION; DENDRITIC CELLS;
D O I
10.1074/jbc.M110.210575
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Innate cellular immunity is the immediate host response against pathogens, and activation of innate immunity also modulates the induction of adaptive immunity. The nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are a family of intracellular receptors that recognize conserved patterns associated with intracellular pathogens, but information about their role in the host defense against DNA viruses is limited. Here we report that varicella-zoster virus (VZV), an alphaherpesvirus that is the causative agent of varicella and herpes zoster, induces formation of the NLRP3 inflammasome and the associated processing of the proinflammatory cytokine IL-1 beta by activated caspase-1 in infected cells. NLRP3 inflammasome formation was induced in VZV-infected human THP-1 cells, which are a transformed monocyte cell line, primary lung fibroblasts, and melanoma cells. Absent in melanoma gene-2 (AIM2) is an interferon-inducible protein that can form an alternative inflammasome complex with caspase-1 in virus-infected cells. Experiments in VZV-infected melanoma cells showed that NLRP3 protein recruits the adaptor protein ASC and caspase-1 to form an NLRP3 inflammasome complex independent of AIM2 protein and in the absence of free radical reactive oxygen species release. NLRP3 was also expressed extensively in infected skin xenografts in the severe combined immunodeficiency mouse model of VZV pathogenesis in vivo. We conclude that NLRP3 inflammasome formation is an innate cellular response to infection with this common pathogenic human herpesvirus.
引用
收藏
页码:17921 / 17933
页数:13
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