Porcine transmissible gastroenteritis virus nonstructural protein 2 contributes to inflammation via NF-κB activation

Abstract

2018) Porcine transmissible gastroenteritis virus nonstructural protein 2 contributes to inflammation via NF-κB activation, ABSTRACT Transmissible gastroenteritis virus (TGEV) infection causes acute enteritis in swine of all ages, and especially in suckling piglets. Small intestinal inflammation is considered a central event in the pathogenesis of TGEV infections, and nuclear factor-kappa B (NF-κB) is a key transcription factor in the inflammatory response. However, it is unclear whether NF-κB is crucial for inducing inflammation during a TGEV infection. Our results show that NF-κB was activated in swine testicular (ST) cells and intestinal epithelial cell lines J2 (IPEC-J2) cells infected with TGEV, which is consistent with the up-regulation of pro-inflammatory cytokines. Treatment of TGEV-infected ST cells and IPEC-J2 cells with the NF-κB-specific inhibitor caused the down-regulation of pro-inflammatory cytokine expression, but did not significantly affect TGEV replication. Individual TGEV protein screening results demonstrated that Nsp2 exhibited a high potential for activating NF-κB and enhancing the expression of pro-inflammatory cytokines. Functional domain analyzes indicated that the first 120 amino acid residues of Nsp2 were essential for NF-κB activation. Taken together, these data suggested that NF-κB activation was a major contributor to TGEV infection-induced inflammation, and that Nsp2 was the key viral protein involved in the regulation of inflammation, with amino acids 1-120 playing a critical role in activating NF-κB. Abbreviations: TCID50: 50% tissue culture infectious dose; DMEM: Dulbecco's Modified Eagle Medium; eNOS: Endothelial nitric oxide synthase; FBS: fetal bovine serum; IFA: Indirect immunofluorescence; IκB: inhibitor of nuclear factor kappa-B; IL: interleukin; IPEC-J2: intestinal epithelial cell

Transmissible Gastroenteritis Virus Infection Up-Regulates FcRn Expression via Nucleocapsid Protein and Secretion of TGF-β in Porcine Intestinal Epithelial Cells

“…The proteins 3a, nsp1, and nsp5 also enhance but have little influence on NF-κB promoter activity. While nsp2 and nsp14 are also potential NF-κB activators, consistent with that reported in previous studies (Zhou et al, 2017;Wang et al, 2018). Since the essential and multifunctional N protein is fundamental for immune regulation and pathogenesis, we examined it more closely.…”

“…TGEV infection has been reported to activate the mitogen-activated protein kinase (MAPK) pathway and destroy epithelial barrier integrity in IPEC-J2 cells (Zhao et al, 2014). TGEV N, nsp2 and nsp14 proteins all induce NF-κB activation (Zhou et al, 2017;Wang et al, 2018;Zhang et al, 2018), but the regulatory mechanism of FcRn is still unknown. Most studies on TGEV have focused on the induction and activation of NF-κB and IFN, but host cell biology may affect cell function.…”

Nonstructural protein 6 of porcine epidemic diarrhea virus induces autophagy to promote viral replication via the PI3K/Akt/mTOR axis

“…The severe inflammatory response induced by viral infection is one of the causes of rapid host death (Wang et al, 2018b). It was reported H. Lin, et al Veterinary Microbiology 244 (2020) 108684 that transmissible gastroenteritis virus (TGEV) infection activates the NF-κB pathway in porcine intestinal epithelial cells and results in severe inflammation (Wang et al, 2018a). The differentially expressed mRNAs and ncRNAs in mock-and TGEV-infected IPEC-J2 cells were primarily enriched in inflammation-related pathways, and ssc_circ_009380 promoted the activation of the NF-κB pathway by binding to miR-22 during TGEV-induced inflammation (Ma et al, 2018).…”

Identification and analysis of long non-coding RNAs that are involved in inflammatory process in response to transmissible gastroenteritis virus infection

“…In our data, many neighbouring genes correspond to compartments of the inflammatory response, such as PML (ENSSSCT00000002141), Interferon Beta 1 (IFNB1) (ENSSSCT00000005691), Radical S-Adenosyl methionine domain containing 2 (RSAD2) (ENSSSCT00000009461), and interferon induced protein with tetratricopeptide repeats 5 (IFIT5) (ENSSSCT00000011440). Previous studies have shown that NF-κB signaling pathway, one of the most important pathways, plays an important role during TGEVinduced inflammatory response [9,16,39,40]. Therefore, changes in the expression levels of genes, which related in NF-κB signaling pathway, might influence the TGEV-induced inflammatory response.…”