PLC-gamma 1 is involved in the inflammatory response induced by influenza A virus H1N1 infection
PLC-gamma 1 is involved in the inflammatory response induced by influenza A virus H1N1 infection
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PLC-gamma 1参与甲型H1N1流感病毒感染引起的炎症反应
DOI：
10.1016/j.virol.2016.06.003
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Zhu Qiyun
中科院分区：
文献类型：
--
作者：
Zhu Liqian;Yuan Chen;Ding Xiuyan;Xu Shuai;Yang Jiayun;Liang Yuying;Zhu Qiyun
我们以前曾报道，磷酸肌醇特异性磷脂酶γ1（PLC-γ1）信号被激活的流感病毒H1N1感染，并介导有效的病毒进入人类上皮细胞。在这项研究中，我们发现，H1N1也激活PLCγ-1信号在人前单核细胞系衍生的巨噬细胞。令人惊讶的是，激活的PLCγ-1信号对病毒在巨噬细胞中的复制并不重要，但参与了病毒诱导的炎症反应。PLC-γ1特异性抑制剂U 73122可显著抑制H1N1病毒诱导的NF-κB信号通路，阻断TNF-α、IL-6、MIP-1α和活性氧化物质的上调。在上皮细胞和巨噬细胞系中，IL-1β和TNF-α在正反馈回路中激活PLCγ-1信号传导。综上所述，我们首次证明PLCγ-1信号在H1N1诱导的炎症反应中起重要作用。我们的研究表明，针对PLCγ-1信号转导是一种潜在的抗H1N1病毒治疗，通过抑制病毒复制和过度炎症。
We have previously reported that phosphoinositide-specific phospholipase γ1 (PLC-γ1) signaling is activated by influenza virus H1N1 infection and mediates efficient viral entry in human epithelial cells. In this study, we show that H1N1 also activates PLCγ-1 signaling in human promonocytic cell line -derived macrophages. Surprisingly, the activated PLCγ-1 signaling is not important for viral replication in macrophages, but is involved in the virus-induced inflammatory responses. PLC-γ1-specific inhibitor U73122 strongly inhibits the H1N1 virus-induced NF-κB signaling, blocking the up-regulation of TNF-α, IL-6, MIP-1α, and reactive oxidative species. In a positive feedback loop, IL-1β and TNF-α activate the PLCγ-1 signaling in both epithelial and macrophage cell lines. In summary, we have shown for the first time that the PLCγ-1 signaling plays an important role in the H1N1-induced inflammatory responses. Our study suggests that targeting the PLCγ-1 signaling is a potential antiviral therapy against H1N1 by inhibiting both viral replication and excessive inflammation.