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

Open access
Huang, Zhe, Wu, Su-Qin, Liang, Yaoji, Zhou, Xiaojuan, Chen, Wanze, Li, Lisheng, Wu, Jianfeng, Zhuang, Qiuyu, Chen, Chang’an, Li, Jingxian, Zhong, Chuan-Qi, Xia, Weixiang, Zhou, Rongbin, Zheng, Chunfu, Han, Jiahuai·2015·Cell Host & Microbe

Abstract

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.

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Metadata

Authors
Huang, Z., Wu, S.-Q., Liang, Y., Zhou, X., Chen, W., Li, L., Wu, J., Zhuang, Q., Chen, C., Li, J., Zhong, C.-Q., Xia, W., Zhou, R., Zheng, C., & Han, J.
Venue
Cell Host & Microbe
Publisher
Elsevier BV
Published
2015-02
Volume
17
Issue
2
Pages
229-242
ISSN
1931-3128 (ISSN-L)
OpenAlex
W2071769633
Cited by
267
References
5
FWCI
21.56
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: RIP1/RIP3 Binding to HSV-1 ICP6 Initiates Necroptosis to Restrict Virus Propagation in Mice. https://app.cochat.ai/papers/10.1016/j.chom.2015.01.002
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Huang, Z., Wu, S.-Q., Liang, Y., Zhou, X., Chen, W., Li, L., Wu, J., Zhuang, Q., Chen, C., Li, J., Zhong, C.-Q., Xia, W., Zhou, R., Zheng, C., & Han, J. (2015). RIP1/RIP3 Binding to HSV-1 ICP6 Initiates Necroptosis to Restrict Virus Propagation in Mice. Cell Host & Microbe. https://doi.org/10.1016/j.chom.2015.01.002

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