RIP1/RIP3 Binding to HSV-1 ICP6 Initiates Necroptosis to Restrict Virus Propagation in Mice

被引：221

作者：

Huang, Zhe ^{[1
]}

Wu, Su-Qin ^{[1
]}

Liang, Yaoji ^{[1
]}

Zhou, Xiaojuan ^{[1
]}

Chen, Wanze ^{[1
]}

Li, Lisheng ^{[1
]}

Wu, Jianfeng ^{[1
]}

Zhuang, Qiuyu ^{[1
]}

Chen, Chang'an ^{[1
]}

Li, Jingxian ^{[1
]}

Zhong, Chuan-Qi ^{[1
]}

Xia, Weixiang ^{[1
]}

Zhou, Rongbin ^{[2
]}

Zheng, Chunfu ^{[3
,4
]}

Han, Jiahuai ^{[1
]}

机构：

[1] Xiamen Univ, Sch Life Sci, Innovat Ctr Cell Signaling Network, State Key Lab Cellular Stress Biol, Xiamen 361005, Fujian, Peoples R China

[2] Univ Sci & Technol China, Sch Life Sci, Innovat Ctr Cell Signaling Network, Hefei 230026, Anhui, Peoples R China

[3] Soochow Univ, Inst Biol, Suzhou, Jiangsu, Peoples R China

[4] Soochow Univ, Inst Med Sci, Suzhou, Jiangsu, Peoples R China

来源：

CELL HOST & MICROBE | 2015年 / 17卷 / 02期

关键词：

MIXED LINEAGE KINASE; DOMAIN-LIKE PROTEIN; VIRAL RIBONUCLEOTIDE REDUCTASE; CYTOSOLIC DNA SENSOR; CELL-DEATH; PROGRAMMED NECROSIS; RIP3; PATHWAY; PHOSPHORYLATION; DOWNSTREAM;

D O I：

10.1016/j.chom.2015.01.002

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Necroptosis is a form of programmed necrosis that is mediated by signaling complexes containing the receptor-interacting protein 3 (RIP3) and RIP1 kinases. We show that RIP3 and its interaction with the herpes simplex virus type 1 (HSV-1) protein ICP6 triggers necroptosis in infected mouse cells and limits viral propagation in mice. ICP6 interacts with RIP1/RIP3 through its RHIM domain and forms dimers/oliogmers by its C-terminal R1 domain. These binding events result in RIP1-RIP3 hetero-and RIP3-RIP3 homo-interactions and subsequent necroptosis of HSV-1-infected mouse cells. However, ICP6 RHIM cannot trigger necroptosis and even inhibits TNF-induced necroptosis in human cells. As the RHIM domain in murine cytomegalovirus protein vIRA can inhibit necroptosis in both human and mouse cells, these data suggest that both viral and host RHIM sequences determine whether the virus-host RHIM interaction is pro-or anti-necroptotic and that some viruses may evolve to escape this restriction.

引用

页码：229 / 242

页数：14

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