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.
Bibliographical noteFunding Information:
The authors are grateful to Dr. Ze Chen, Shanghai Institute of Biological Products for providing the influenza virus PR8, to Dr. Yuwei Gao, Military Veterinary Research Institute, Academy of Military Medical Sciences of China for providing pdm09 H1N1 virus, and to Dr. Hai Yu, Shanghai Veterinary Research Institute, CAAS for providing the A549 cells and MDCK cells. We kindly acknowledge the funding support for the study provided by Chinese National Science Foundation Grant (Nos. 31472172 and 81571998 ), State Key Laboratory of Veterinary Etiological Biology ( SKLVEB2014KFKT005 ) and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).
© 2016 Elsevier Inc.
- Influenza A virus
- Pro-inflammatory cytokines