PLC-γ1 is involved in the inflammatory response induced by influenza A virus H1N1 infection

We have previously reported that phosphoinositide-specific phospholipase gamma 1 (PLC-gamma 1) 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 PLC gamma-1 signaling in human promonocytic cell line-derived macrophages. Surprisingly, the activated PLC gamma-1 signaling is not important for viral replication in macrophages, but is involved in the virus-induced inflammatory responses. PLC-gamma 1-specific inhibitor U73122 strongly inhibits the H1N1 virus-induced NF-kappa B signaling, blocking the up-regulation of TNF-alpha, IL-6, MIP-1 alpha, and reactive oxidative species. In a positive feedback loop, IL-1 beta and TNF-alpha activate the PLC gamma-1 signaling in both epithelial and macrophage cell lines. In summary, we have shown for the first time that the PLC gamma-1 signaling plays an important role in the H1N1-induced inflammatory responses. Our study suggests that targeting the PLC gamma-1 signaling is a potential antiviral therapy against H1N1 by inhibiting both viral replication and excessive inflammation. (C) 2016 Elsevier Inc. All rights reserved.