RIPK3 Activates Parallel Pathways of MLKL-Driven Necroptosis and FADD-Mediated Apoptosis to Protect against Influenza A Virus.
RIPK3 Activates Parallel Pathways of MLKL-Driven Necroptosis and FADD-Mediated Apoptosis to Protect against Influenza A Virus.
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DOI：
10.1016/j.chom.2016.05.011
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发表时间：
2016-07-13
影响因子：
30.3
通讯作者：
Balachandran S
中科院分区：
文献类型：
--
作者：
Nogusa S;Thapa RJ;Dillon CP;Liedmann S;Oguin TH 3rd;Ingram JP;Rodriguez DA;Kosoff R;Sharma S;Sturm O;Verbist K;Gough PJ;Bertin J;Hartmann BM;Sealfon SC;Kaiser WJ;Mocarski ES;López CB;Thomas PG;Oberst A;Green DR;Balachandran S
甲型流感病毒（IAV）是在许多细胞类型的原代培养物和体内的裂解病毒。我们报告说，激酶RIPK 3是必不可少的IAV诱导的哺乳动物成纤维细胞和肺上皮细胞裂解。复制IAV驱动含有RIPK 3的复合物的组装，该复合物包括激酶RIPK 1、假激酶MLKL和衔接蛋白FADD，并且独立于RNA传感先天免疫受体（RLR、TLR、PKR）或细胞因子的信号传导而形成I型干扰素和TNF-α。在RIPK 3的下游，IAV激活MLKL驱动的坏死性凋亡和FADD介导的细胞凋亡的平行途径，前者依赖于RIPK 3激酶活性，而不依赖于RIPK 1活性。RIPK 3缺陷或MLKL和FADD双重缺陷的小鼠，但不是单独的MLKL，比野生型小鼠更易感染IAV，揭示了RIPK 3介导的细胞凋亡在抗病毒免疫中的重要作用。总的来说，这些结果概述了RIPK 3激活的细胞溶解机制，对控制呼吸道IAV感染至关重要。
Influenza A virus (IAV) is a lytic virus in primary cultures of many cell types and in vivo. We report that the kinase RIPK3 is essential for IAV-induced lysis of mammalian fibroblasts and lung epithelial cells. Replicating IAV drives assembly of a RIPK3-containing complex that includes the kinase RIPK1, the pseudokinase MLKL, and the adaptor protein FADD, and forms independently of signaling by RNA-sensing innate immune receptors (RLRs, TLRs, PKR), or the cytokines type I interferons and TNF-α. Downstream of RIPK3, IAV activates parallel pathways of MLKL-driven necroptosis and FADD-mediated apoptosis, with the former reliant on RIPK3 kinase activity and neither on RIPK1 activity. Mice deficient in RIPK3 or doubly-deficient in MLKL and FADD, but not MLKL alone, are more susceptible to IAV than their wild-type counterparts, revealing an important role for RIPK3-mediated apoptosis in antiviral immunity. Collectively, these results outline RIPK3-activated cytolytic mechanisms essential for controlling respiratory IAV infection.
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影响因子：
16
作者：
Mandal P;Berger SB;Pillay S;Moriwaki K;Huang C;Guo H;Lich JD;Finger J;Kasparcova V;Votta B;Ouellette M;King BW;Wisnoski D;Lakdawala AS;DeMartino MP;Casillas LN;Haile PA;Sehon CA;Marquis RW;Upton J;Daley-Bauer LP;Roback L;Ramia N;Dovey CM;Carette JE;Chan FK;Bertin J;Gough PJ;Mocarski ES;Kaiser WJ
通讯作者：
Kaiser WJ
影响因子：
64.8
作者：
Kash, John C.;Tumpey, Terrence M.;Katze, Michael G.
通讯作者：
Katze, Michael G.
影响因子：
5.3
作者：
Po, JLZ;Gardner, EM;Murasko, DM
通讯作者：
Murasko, DM
影响因子：
12.4
作者：
Cook, W. D.;Moujalled, D. M.;Vaux, D. L.
通讯作者：
Vaux, D. L.
影响因子：
4.2
作者：
Harris, Philip A.;Bandyopadhyay, Deepak;Gough, Peter J.
通讯作者：
Gough, Peter J.