Herpes Simplex Virus 1 (HSV-1) and HSV-2 Mediate Species-Specific Modulations of Programmed Necrosis through the Viral Ribonucleotide Reductase Large Subunit R1
Herpes Simplex Virus 1 (HSV-1) and HSV-2 Mediate Species-Specific Modulations of Programmed Necrosis through the Viral Ribonucleotide Reductase Large Subunit R1
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单纯疱疹病毒 1 (HSV-1) 和 HSV-2 通过病毒核糖核苷酸还原酶大亚基 R1 介导程序性坏死的物种特异性调节
DOI：
10.1128/jvi.02446-15
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发表时间：
2015-11
影响因子：
5.4
通讯作者：
Sudan He
中科院分区：
文献类型：
--
作者：
Xiaoliang Yu;Yun Li;Qin Chen;Chenhe Su;Zili Zhang;Chengkui Yang;Zhilin Hu;Jue Hou;Jinying Zhou;Ling Gong;Xuejun Jiang;Chunfu Zheng;Sudan He
受体相互作用蛋白激酶3（RIP 3）及其底物混合谱系激酶结构域样蛋白（MLKL）是程序性坏死的核心调节因子。通过程序性坏死消除病原体感染的细胞是宿主重要的防御机制。在这里，我们报告说，人类单纯疱疹病毒1型（HSV-1）和HSV-2有相反的影响，在人类细胞的程序性坏死与它们的影响，在小鼠细胞。与HSV-1相似，HSV-2感染引发小鼠细胞的程序性坏死。然而，HSV-1和HSV-2感染都不能诱导人类细胞的程序性坏死。此外，HSV-1或HSV-2感染人细胞通过阻止RIP 1/RIP 3坏死体的诱导来阻断肿瘤坏死因子（TNF）诱导的坏死。HSV核糖核苷酸还原酶大亚基R1足以抑制TNF诱导的坏死，并且需要其RIP同型相互作用基序（RHIM）结构域来破坏人类细胞中的RIP 1/RIP 3复合物。因此，这项研究提供了证据表明，HSV可能已经进化出了逃避人类细胞程序性坏死的宿主防御机制的策略。重要性这项研究表明，感染HSV-1和HSV-2阻断TNF诱导的人细胞坏死，而这些病毒直接激活小鼠细胞的程序性坏死。HSV R1的表达抑制TNF诱导的人细胞坏死。R1的RHIM结构域对于其与人RIP 3和RIP 1的结合是必需的，导致RIP 1/RIP 3复合物的破坏。这项研究为HSV对程序性坏死的物种特异性调节提供了新的见解。
ABSTRACT Receptor-interacting protein kinase 3 (RIP3) and its substrate mixed-lineage kinase domain-like protein (MLKL) are core regulators of programmed necrosis. The elimination of pathogen-infected cells by programmed necrosis acts as an important host defense mechanism. Here, we report that human herpes simplex virus 1 (HSV-1) and HSV-2 had opposite impacts on programmed necrosis in human cells versus their impacts in mouse cells. Similar to HSV-1, HSV-2 infection triggered programmed necrosis in mouse cells. However, neither HSV-1 nor HSV-2 infection was able to induce programmed necrosis in human cells. Moreover, HSV-1 or HSV-2 infection in human cells blocked tumor necrosis factor (TNF)-induced necrosis by preventing the induction of an RIP1/RIP3 necrosome. The HSV ribonucleotide reductase large subunit R1 was sufficient to suppress TNF-induced necrosis, and its RIP homotypic interaction motif (RHIM) domain was required to disrupt the RIP1/RIP3 complex in human cells. Therefore, this study provides evidence that HSV has likely evolved strategies to evade the host defense mechanism of programmed necrosis in human cells. IMPORTANCE This study demonstrated that infection with HSV-1 and HSV-2 blocked TNF-induced necrosis in human cells while these viruses directly activated programmed necrosis in mouse cells. Expression of HSV R1 suppressed TNF-induced necrosis of human cells. The RHIM domain of R1 was essential for its association with human RIP3 and RIP1, leading to disruption of the RIP1/RIP3 complex. This study provides new insights into the species-specific modulation of programmed necrosis by HSV.
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影响因子：
30.3
作者：
J. Upton;W. Kaiser;E. Mocarski
通讯作者：
J. Upton;W. Kaiser;E. Mocarski
影响因子：
4.8
作者：
Kaiser, William J.;Sridharan, Haripriya;Mocarski, Edward S.
通讯作者：
Mocarski, Edward S.
影响因子：
56.9
作者：
Zhang, Duan-Wu;Shao, Jing;Han, Jiahuai
通讯作者：
Han, Jiahuai
影响因子：
64.5
作者：
Wang, Zhigao;Jiang, Hui;Wang, Xiaodong
通讯作者：
Wang, Xiaodong
影响因子：
5.4
作者：
Dobbelstein, M;Shenk, T
通讯作者：
Shenk, T