The role of phospholipase C signaling in bovine herpesvirus 1 infection

Liqian Zhu,Guoqiang Zhu,Chen Yuan,Xiuyan Ding,Clinton Jones

doi:10.1186/s13567-017-0450-5

Liqian Zhu, Guoqiang Zhu + Show 3 more

Open Access

https://doi.org/10.1186/s13567-017-0450-5

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Journal: Veterinary Research	Publication Date: Sep 7, 2017
Citations: 45	License type: open-access

Affiliation: Oklahoma State University, Yangzhou University

Abstract

Bovine herpesvirus 1 (BoHV-1) infection enhanced the generation of inflammatory mediator reactive oxidative species (ROS) and stimulated MAPK signaling that are highly possibly related to virus induced inflammation. In this study, for the first time we show that BoHV-1 infection manipulated phospholipase C (PLC) signaling, as demonstrated by the activation of PLCγ-1 at both early stages [at 0.5 h post-infection (hpi)] and late stages (4–12 hpi) during the virus infection of MDBK cells. Viral entry, and de novo protein expression and/or DNA replication were potentially responsible for the activation of PLCγ-1 signaling. PLC signaling inhibitors of both U73122 and edelfosine significantly inhibited BoHV-1 replication in both bovine kidney cells (MDBK) and rabbit skin cells (RS-1) in a dose-dependent manner by affecting the virus entry stage(s). In addition, the activation of Erk1/2 and p38MAPK signaling, and the enhanced generation of ROS by BoHV-1 infection were obviously ameliorated by chemical inhibition of PLC signaling, implying the requirement of PLC signaling in ROS production and these MAPK pathway activation. These results suggest that the activation of PLC signaling is a potential pathogenic mechanism for BoHV-1 infection.

Highlights

Bovine Herpesvirus 1 (BoHV-1) is an enveloped virus belonging to Alphaherpesvirinae subfamily member [1]
phospholipase C (PLC) signaling inhibitors U73122 and edelfosine inhibited BoHV‐1 infection in bovine kidney cells (MDBK cells) and rabbit skin cells (RS‐1 cells) To test whether PLC signaling is involved in BoHV-1 infection, the effect of chemical inhibition of PLC signaling on viral replication in MDBK cells was first investigated
The known herpesvirus inhibitor ACY at a concentration of 50 μM decreased the virus titer of ~1-log compared to the control (Figure 1F), which validated the inhibitory effects of both U73122 and edelfosine on BoHV-1 replication in RS-1 cells

Summary

Introduction

Bovine Herpesvirus 1 (BoHV-1) is an enveloped virus belonging to Alphaherpesvirinae subfamily member [1]. It is known that BoHV-1 infection induces overexpression of pro-inflammatory cytokines, such as IL-1β and TNF-α that contribute greatly to the inflammatory response [7, 8]. We recently identified that BoHV-1 infection increases the generation of inflammatory mediator, reactive oxidative species (ROS) [9], which is a potential mechanism to promote inflammatory response. Over-produced ROS mediated inflammatory response by diverse mechanisms in varied virus infections. The activation of p38MAPK and Erk1/2 signaling by BoHV-1 infection is not mediated by over-produced ROS [14], Zhu et al Vet Res (2017) 48:45 though BoHV-1 and HSV-1 are genetically closed [9]. How BoHV-1 infection contributes to ROS production and the activation of p38MAPK and Erk1/2 signaling has yet to be found

Methods

Results

Conclusion