PLC-γ1 is involved in the inflammatory response induced by influenza A virus H1N1 infection.
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.
College of Veterinary Medicine, Yangzhou University and Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, 48 Wenhui East Road, Yangzhou 225009, China.
Liqian
L
Zhu
College of Veterinary Medicine, Yangzhou University and Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, 48 Wenhui East Road, Yangzhou 225009, China.
Chen
C
Yuan
College of Veterinary Medicine, Yangzhou University and Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, 48 Wenhui East Road, Yangzhou 225009, China.
Xiuyan
X
Ding
The State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 1 Xujiaping, Chengguan District, Lanzhou 730046, Gansu, China.
Shuai
S
Xu
The State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 1 Xujiaping, Chengguan District, Lanzhou 730046, Gansu, China.
Jiayun
J
Yang
Department of Veterinary and Biomedical Sciences, University of Minnesota, Twin Cities, MN 55108, USA. Electronic address: liangy@umn.edu.
Yuying
Y
Liang
The State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 1 Xujiaping, Chengguan District, Lanzhou 730046, Gansu, China. Electronic address: zhuqiyun@caas.cn.
Qiyun
Q
Zhu
D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004963:Estrenes / Q000494:pharmacology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D053118:Influenza A Virus, H1N1 Subtype / Q000502:physiology*; D007251:Influenza, Human / Q000378:metabolism* / Q000821:virology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D016328:NF-kappa B / Q000378:metabolism; D051966:Phospholipase C gamma / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011760:Pyrrolidinones / Q000494:pharmacology; D017382:Reactive Oxygen Species; D015398:Signal Transduction / Q000187:drug effects; D020298:U937 Cells
D016207:Cytokines; D004963:Estrenes; D018836:Inflammation Mediators; D016328:NF-kappa B; D011760:Pyrrolidinones; D017382:Reactive Oxygen Species; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D051966:Phospholipase C gamma
H1N1; Inflammation; Influenza A virus; Macrophage; PLC-γ1; Pro-inflammatory cytokines; ROS