Necroptosis: The Trojan horse in cell autonomous antiviral host defense.

Necroptosis: The Trojan horse in cell autonomous antiviral host defense.
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DOI:
10.1016/j.virol.2015.03.016
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发表时间:
2015-05
期刊:
影响因子:
3.7
通讯作者:
Kaiser, William J.
Kaiser, William J.
中科院分区:
医学3区
文献类型:
--
作者:
Mocarski, Edward S.;Guo, Hongyan;Kaiser, William J.

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疱疹病毒抑制细胞死亡,以确保在其自然宿主中持续感染。小鼠巨细胞病毒(MCMV)编码凋亡抑制因子和m45编码的RIP激活病毒抑制剂(vIRA),阻断RIP同型相互作用基序(RHIM)信号传导和RIP3(也称为RIPK3)的募集,以防止坏死。MCMV和人巨细胞病毒编码一种caspase (Casp)8激活的病毒抑制剂,以阻止细胞凋亡,这种活性释放坏死坏死。单纯疱疹病毒(HSV)1和HSV2分别在ul39编码的ICP6和ICP10中采用RHIM和Casp8抑制策略,它们是MCMV M45的疱疹病毒保守同源物。两种HSV蛋白通过阻断Casp8活性,同时阻止rhm依赖性RIP3激活和死亡,使人细胞对坏死坏死敏感。在小鼠细胞中,HSV1 ICP6与RIP3相互作用,令人惊讶的是,它会导致坏死。因此,疱疹病毒已经阐明了自然宿主中死亡对宿主防御的贡献,以及它在非自然宿主中限制跨物种感染的潜力。
Herpesviruses suppress cell death to assure sustained infection in their natural hosts. Murine cytomegalovirus (MCMV) encodes suppressors of apoptosis as well as M45-encoded viral inhibitor of RIP activation (vIRA) to block RIP homotypic interaction motif (RHIM)-signaling and recruitment of RIP3 (also called RIPK3), to prevent necroptosis. MCMV and human cytomegalovirus encode a viral inhibitor of caspase (Casp)8 activation to blocks apoptosis, an activity that unleashes necroptosis. Herpes simplex virus (HSV)1 and HSV2 incorporate both RHIM and Casp8 suppression strategies within UL39-encoded ICP6 and ICP10, respectively, which are herpesvirus-conserved homologs of MCMV M45. Both HSV proteins sensitize human cells to necroptosis by blocking Casp8 activity while preventing RHIM-dependent RIP3 activation and death. In mouse cells, HSV1 ICP6 interacts with RIP3 and, surprisingly, drives necroptosis. Thus, herpesviruses have illuminated the contribution of necoptosis to host defense in the natural host as well as its potential to restrict cross-species infections in nonnatural hosts.
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