A comparison of the impact of Shimen and C strains of classical swine fever virus on Toll-like receptor expression

Abstract

Classical swine fever is one of the most important swine diseases worldwide and has tremendous socioeconomic impact. In this study, we focused on the signalling pathways of Toll-like receptors (TLRs) because of their roles in the detection and response to viral infections. To this end, two classical swine fever virus (CSFV) strains, namely the highly virulent CSFV Shimen strain and the avirulent C strain (a vaccine strain), were employed, and the expression of 19 immune effector genes was analysed by real-time PCR, Western blot analyses, ELISA and flow cytometry analyses. In vitro experiments were conducted with porcine monocyte-derived macrophages (pMDMs). The results showed that the mRNA and protein levels of TLR2, TLR4 and TLR7 were upregulated in response to CSFV infection, but TLR3 remained unchanged, and was downregulated after infection with the C strain and the Shimen virus, respectively. Furthermore, TLR3-mediated innate immune responses were inhibited in Shimen-strain-infected pMDMs by stimulation with poly(I : C). Accordingly, comprehensive analyses were performed to detect TLR-dependent cytokine responses and the activation of TLR signalling elements. CSFV infection induced mitogen-activated protein kinase activation, but did not elicit NFκB activation, thereby affecting the production of pro-inflammatory cytokines. The Shimen strain infection resulted in a significant activation of IFN regulatory factor IRF7 and suppression of IRF3. These data provided clues for understanding the effect of CSFV infection on the TLR-mediated innate immune response and associated pathological changes.

Classical Swine Fever Virus Infection and Its NS4A Protein Expression Induce IL-8 Production through MAVS Signaling Pathway in Swine Umbilical Vein Endothelial Cells

“…In addition, the increase of ROS impacts on the activation of NF-κB, MAPK ERK, JNK, p38, and PI3K-Akt signaling pathways (Thannickal and Fanburg, 2000 ; Kyaw et al, 2001 ; Qadri et al, 2004 ; Groeger et al, 2009 ; Yi et al, 2015 ; Zhang et al, 2016 ). However, CSFV fails to activate the NF-κB-signaling pathway (Chen et al, 2012 ; Cao et al, 2015 ). Thus, we speculated that CSFV may induce IL-8 production through ROS-mediated ERK, JNK, p38, or PI3K-Akt pathways, and the hypothesis will be further studied in future research.…”

Infection with Classical Swine Fever Virus Induces Expression of Type III Interferons and Activates Innate Immune Signaling

“…TLR-7 binds with the ssRNA derived from CSFV and TLR-3 senses the replication intermediate dsRNAs ( Diebold et al, 2004 ; Sen and Sarkar, 2005 ; Chen et al, 2015 ). Intracellular detection of ssRNA by TLR-7 triggers the activation of transcription factors IRF-7 and NF-κB, which ultimately initiate the expression of type I IFNs including IFNα and IFNβ ( Lund et al, 2004 ; Cao et al, 2015 ). TLR-3 signaling activates the transcription factor IRF-3, which induces expression of the IFN-β and type III IFNs upon its entrance into the nucleus of cells ( Kawai and Akira, 2006 ; Chen et al, 2015 ).…”

TRAF6 is a novel NS3-interacting protein that inhibits classical swine fever virus replication

“…We also revealed that CSFV Shimen infection of pMDMs leads to the activation of MAPK signalling pathways, while it fails to activate NF-κB. Furthermore, the Shimen infection reduces interferon regulatory factor (IRF)3 expression, but enhances IRF7 expression, thereby affecting the production of type I IFN responses 21 . HCV infection suppresses host innate immune response by degrading TRAF6 23 .…”

“…Viruses elicit the expression and release of a range of cytokines via the NF-κB-signalling pathway as part of the primary host defense mechanism. A previous study reported that CSFV failed to activate the NF-κB-signalling pathway 20 , 21 . Our findings showed that TRAF6 overexpression promoted NF-κB activation, and resulted in upregulation of IFN-β and IL-6 expression in PAMs.…”