Coordinated expression of vascular endothelial growth factor A and urokinase-type plasminogen activator contributes to classical swine fever virus Shimen infection in macrophages

Xiaocheng Gong,Xi Zuo,Zhongxing Wu,Xuepeng Li,Aoxue Hu,Jun He,Pengbo Ning

doi:10.1186/s12917-019-1826-8

Abstract

BackgroundThe Shimen strain of classical swine fever (CSF) virus (CSFV) causes CSF, which is mainly characterised by disseminated intravascular haemorrhage. Macrophages are an essential component of innate immunity against pathogenic microorganisms; however, the role of macrophages in CSF pathogenesis remains unclear. To illuminate the infective mechanism of CSFV, we used gene co-expression networks derived from macrophages infected with CSFV Shimen and CSFV C as well as uninfected macrophages to screen key regulatory genes, and their contributions to the pathogenesis of CSF were discussed.ResultsVascular endothelial growth factor A (VEGFA) and plasminogen activator, urokinase (PLAU, which encodes urokinase-type plasminogen activator [uPA]) were identified as coordinated genes expressed in macrophages by gene co-expression networks. Quantitative polymerase chain reaction and western blot analysis confirmed that VEGFA and PLAU were significantly up-regulated at both the transcription and translation levels after infection. Further, confocal microscopy analysis proposed that the VEGFA and uPA proteins were temporally co-localised with the CSFV protein E2.ConclusionsOur findings suggest that co-expression of VEGFA and PLAU in macrophages contributes to CSFV Shimen infection and serves as a significant avenue for the strain to form an inflammatory microenvironment, providing new insight into the mechanisms of CSF caused by a virulent strain.

Highlights

The Shimen strain of classical swine fever (CSF) virus (CSFV) causes CSF, which is mainly characterised by disseminated intravascular haemorrhage
Vascular endothelial growth factor A (VEGFA) and Plasminogen activator (PLAU) expression are positively correlated with classical swine fever virus (CSFV) Shimen infection To understand the molecular changes caused by CSFV Shimen, we used significantly up- and down-regulated genes from the digital gene expression (DGE) database to construct a co-expression network of the CSFV Shimen vs CSFV C and control groups, and a network diagram shows this in detail
Up-regulation of VEGFA and PLAU by CSFV Shimen infection in macrophages As shown in Fig. 2a, DGE analysis showed VEGFA and PLAU to be significantly up-regulated in CSFV Shimen-infected macrophages compared to those in CSFV C-infected and control macrophages. quantitative polymerase chain reaction (qPCR) confirmed infection with either CSFV Shimen or CSFV

Summary

Introduction

The Shimen strain of classical swine fever (CSF) virus (CSFV) causes CSF, which is mainly characterised by disseminated intravascular haemorrhage. Macrophages are an essential component of innate immunity against pathogenic microorganisms; the role of macrophages in CSF pathogenesis remains unclear. The Shimen strain of classical swine fever virus (CSFV) causes an especially infectious disease in domestic pigs known as classical swine fever (CSF), which has been listed as a highly contagious disease by the World Organisation for Animal Health [1]. Tumours and inflammatory disorders often trigger pathological angiogenesis to generate a new vascular supply; detailed pathological studies have revealed the VEGFs as active participants in these processes [2]. The role of VEGFA in different inflammatory diseases has been explored, and the blockade of its signalling is considered a protective strategy in the treatment of such diseases [4]. In recent years, increased levels of VEGFA have been observed in pro-inflammatory environments created by viral infections in humans [5, 6], further motivating study of VEGFA

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