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

Liqian Zhu; Chen Yuan; Xiuyan Ding; Shuai Xu; Jiayun Yang; Yuying Liang; Qiyun Zhu

doi:10.1016/j.virol.2016.06.003

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

Liqian Zhu, Chen Yuan, Xiuyan Ding, Shuai Xu, Jiayun Yang, Yuying Liang, Qiyun Zhu

Veterinary and Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

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.

Original language	English (US)
Pages (from-to)	131-137
Number of pages	7
Journal	Virology
Volume	496
DOIs	https://doi.org/10.1016/j.virol.2016.06.003
State	Published - Sep 1 2016

Bibliographical note

Funding 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).

Publisher Copyright:
© 2016 Elsevier Inc.

Keywords

H1N1
Inflammation
Influenza A virus
Macrophage
PLC-γ1
Pro-inflammatory cytokines
ROS

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access

10.1016/j.virol.2016.06.003

OpenUrl availability

Full text

Cite this

@article{7bd478bce0fa40d395435c8dd7a33bcc,

title = "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.",

keywords = "H1N1, Inflammation, Influenza A virus, Macrophage, PLC-γ1, Pro-inflammatory cytokines, ROS",

author = "Liqian Zhu and Chen Yuan and Xiuyan Ding and Shuai Xu and Jiayun Yang and Yuying Liang and Qiyun Zhu",

note = "Funding 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). Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

year = "2016",

month = sep,

day = "1",

doi = "10.1016/j.virol.2016.06.003",

language = "English (US)",

volume = "496",

pages = "131--137",

journal = "Virology",

issn = "0042-6822",

publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - PLC-γ1 is involved in the inflammatory response induced by influenza A virus H1N1 infection

AU - Zhu, Liqian

AU - Yuan, Chen

AU - Ding, Xiuyan

AU - Xu, Shuai

AU - Yang, Jiayun

AU - Liang, Yuying

AU - Zhu, Qiyun

N1 - Funding 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). Publisher Copyright: © 2016 Elsevier Inc.

PY - 2016/9/1

Y1 - 2016/9/1

N2 - 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.

AB - 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.

KW - H1N1

KW - Inflammation

KW - Influenza A virus

KW - Macrophage

KW - PLC-γ1

KW - Pro-inflammatory cytokines

KW - ROS

UR - http://www.scopus.com/inward/record.url?scp=84973597728&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84973597728&partnerID=8YFLogxK

U2 - 10.1016/j.virol.2016.06.003

DO - 10.1016/j.virol.2016.06.003

M3 - Article

C2 - 27310357

AN - SCOPUS:84973597728

SN - 0042-6822

VL - 496

SP - 131

EP - 137

JO - Virology

JF - Virology

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

Access

OpenUrl availability

Other files and links

Fingerprint

Cite this