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

Abstract

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.

• Authors: Liqian Zhu, Chen Yuan, Xiuyan Ding, Shuai Xu, Jiayun Yang, Yuying Liang, Qiyun Zhu
• Journal: Virology (Virology) Vol. 496 Pg. 131-137 (09 2016) ISSN: 1096-0341 [Electronic] United States
• PMID: 27310357 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Cytokines
• Estrenes
• Inflammation Mediators
• NF-kappa B
• Pyrrolidinones
• Reactive Oxygen Species
• 1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
• Phospholipase C gamma

Topics

• Animals
• Cell Line
• Cytokines (metabolism)
• Estrenes (pharmacology)
• Humans
• Inflammation Mediators (metabolism)
• Influenza A Virus, H1N1 Subtype (physiology)
• Influenza, Human (metabolism, virology)
• Macrophages (drug effects, metabolism, virology)
• NF-kappa B (metabolism)
• Phospholipase C gamma (antagonists & inhibitors, metabolism)
• Pyrrolidinones (pharmacology)
• Reactive Oxygen Species
• Signal Transduction (drug effects)
• U937 Cells