Porcine reproductive and respiratory syndrome virus (PRRSV) induces IL-12p40 production through JNK-AP-1 and NF-κB signaling pathways

Yu, Zhibin; Huang, Chen; Zhang, Qiong; Feng, Wen-hai

doi:10.1016/j.virusres.2016.09.009

Cited by 17 publications

(12 citation statements)

References 55 publications

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“…Using an online promoter scanning utility (http://www-bimas.cit.nih.gov/molbio/proscan/), we found that putative binding motifs for NF-B (TTGAAATTCCCCC) and Sp1 (AGTCAG) are also present in the porcine CD83 promoter, similar to the arrangement in the human and mouse promoters (57). AP-1, Sp1, and NF-B are stimulated by PRRSV infection (58)(59)(60). Sp1 is a regulator of signal transduction and is critically regulated by posttranslational modifications (PTMs), including phosphorylation, methylation, and glycosylation (61).…”

Section: Discussionmentioning

confidence: 86%

The Nucleocapsid Protein and Nonstructural Protein 10 of Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Enhance CD83 Production via NF-κB and Sp1 Signaling Pathways

Chen

Zhang

Bai

et al. 2017

J Virol

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Porcine reproductive and respiratory syndrome, caused by porcine reproductive and respiratory syndrome virus (PRRSV), is a panzootic disease that is one of the most economically costly diseases to the swine industry. A key aspect of PRRSV virulence is that the virus suppresses the innate immune response and induces persistent infection, although the underlying mechanisms are not well understood. The dendritic cell (DC) marker CD83 belongs to the immunoglobulin superfamily and is associated with DC activation and immunosuppression of T cell proliferation when expressed as soluble CD83 (sCD83). In this study, we show that PRRSV infection strongly stimulates CD83 expression in porcine monocyte-derived DCs (MoDCs) and that the nucleocapsid (N) protein and nonstructural protein 10 (nsp10) of PRRSV enhance CD83 promoter activity via the NF-κB and Sp1 signaling pathways. R43A and K44A amino acid substitution mutants of the N protein suppress the N protein-mediated increase of CD83 promoter activity. Similarly, P192-5A and G214-3A mutants of nsp10 (with 5 and 3 alanine substitutions beginning at residues P192 and G214, respectively) abolish the nsp10-mediated induction of the CD83 promoter. Using reverse genetics, four mutant viruses (rR43A, rK44A, rP192-5A, and rG214-3A) and four revertants [rR43A(R), rK44A(R), rP192-5A(R), and rG214-3A(R)] were generated. Decreased induction of CD83 in MoDCs was observed after infection by mutants rR43A, rK44A, rP192-5A, and rG214-3A, in contrast to the results obtained using rR43A(R), rK44A(R), rP192-5A(R), and rG214-3A(R). These findings suggest that PRRSV N and nsp10 play important roles in modulating CD83 signaling and shed light on the mechanism by which PRRSV modulates host immunity. Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically costly pathogens affecting the swine industry. It is unclear how PRRSV inhibits the host's immune response and induces persistent infection. The dendritic cell (DC) marker CD83 belongs to the immunoglobulin superfamily and has previously been associated with DC activation and immunosuppression of T cell proliferation and differentiation when expressed as soluble CD83 (sCD83). In this study, we found that PRRSV infection induces sCD83 expression in porcine MoDCs via the NF-κB and Sp1 signaling pathways. The viral nucleocapsid protein, nonstructural protein 1 (nsp1), and nsp10 were shown to enhance CD83 promoter activity. Amino acids R43 and K44 of the N protein, as well as residues 192 to 196 (P192-5) and 214 to 216 (G214-3) of nsp10, play important roles in CD83 promoter activation. These findings provide new insights into the molecular mechanism of immune suppression by PRRSV.

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Section: Discussionmentioning

confidence: 86%

The Nucleocapsid Protein and Nonstructural Protein 10 of Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Enhance CD83 Production via NF-κB and Sp1 Signaling Pathways

Chen

Zhang

Bai

et al. 2017

J Virol

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“…AP-1 can regulate the expression of multiple genes to respond to multiple stimuli, including cytokines, growth factors, stress, and bacterial and viral infections. Some studies have found that an appropriately high expression of AP-1 can enhance the body's immune and antibacterial ability and improve its ability to respond to multiple stimuli (56). The AP-1 family of transcription factors can activate Toll-like receptor agonists and positively regulate interleukin-4 (IL-4) to activate macrophages, thereby enhancing antibacterial activity (57).…”

Section: Discussionmentioning

confidence: 99%

A Novel lncRNA Regulates the Toll-Like Receptor Signaling Pathway and Related Immune Function by Stabilizing FOS mRNA as a Competitive Endogenous RNA

Fan

Gan

et al. 2019

Front. Immunol.

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Long non-coding RNAs (lncRNAs) have recently emerged as new regulatory molecules with diverse functions in regulating gene expression and significant roles in the immune response. However, the function of many unknown lncRNAs is still unclear. By studying the regulatory effect of daidzein (DA) on immunity, we identified a novel lncRNA with an immune regulatory function: lncRNA- XLOC_098131. In vivo , DA treatment upregulated the expression of lncRNA- XLOC_098131, FOS, and JUN in chickens and affected the expression of activator protein 1 (AP-1) to regulate MAPK signaling, Toll-like receptor signaling, and related mRNA expression. It also enhanced macrophage activity and increased the numbers of blood neutrophils and mononuclear cells, which can improve the body's ability to respond to stress and bacterial and viral infections. Furthermore, DA treatment also reduced B lymphocyte apoptosis and promoted the differentiation of B lymphocytes into plasma cells, which in turn resulted in the production of more immunoglobulins and the promotion of antigen presentation. In vitro , using HEK293FT cells, we demonstrated that mir-548s could bind to and decrease the expression of both FOS and lncRNA- XLOC_098131. LncRNA- XLOC_098131 served as a competitive endogenous RNA to stabilize FOS by competitively binding to miR-548s and thereby reducing its inhibitory effect of FOS expression. Therefore, we concluded that the novel lncRNA XLOC_098131 acts as a key regulatory molecule that can regulate the Toll-like receptor signaling pathway and related immune function by serving as a competitive endogenous RNA to stabilize FOS mRNA expression.

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“…Macrophages could initiate and enhance immune responses through the following two pathways and mediate inflammatory responses (Gajanayaka et al, 2017 ). Firstly, the role of antigen presentation to start immune response; Secondly, the secretion of various types of bioactive substances with immune enhancement effects (Voicu et al, 1994 ; Auray et al, 2016 ; Yu et al, 2016 ), including interferon (IFN-α), interleukin (IL-1β, IL-6, IL-18), chemokines (MCP-1) and receptor (CCR2), adhesion molecules (LFA-1, ICAM-1) (Liu et al, 2015 ), tumor necrosis factor (TNF-α) and antigen presenting molecules (MHC I, II). They could activate the biological function and promote the migration of macrophages.…”

Section: Discussionmentioning

confidence: 99%

The Immunological Regulation Roles of Porcine β-1, 4 Galactosyltransferase V (B4GALT5) in PRRSV Infection

Zhang

Ren

Shi

et al. 2018

Front. Cell. Infect. Microbiol.

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B4GALT5, also known as β-1, 4 galactosyltransferase V, is one of the members of β-1, 4 galactosyltransferase gene (B4GALT) family, which was concerned with embryonic development, tumor generation, other malignant diseases. In this study, we firstly cloned porcine B4GALT (pB4GALT5) from porcine alveolar macrophages, and predicted the structural domain and function of seven porcine β-1, 4 galactosyltransferase (I–VII) based on transcriptome analysis of PRRSV infected cells. Additionally, the upregulated porcine B4GALT5 expression was detected from PRRSV infected porcine alveolar macrophage (PAM) cells. The PRRSV proliferation were slightly inhibited in overexpression of pB4GALT5 transfected cells, the interaction of B4GALT5 and GP5 of PRRSV was firstly be detected by Co-IP, and the co-location between B4GALT5 and GP5 were also observed in golgi membranes by confocal microscopy. A significant increasing mRNA transcription, including inflammatory cytokines (IFN-α, IL-6, IL-18, IL-1β, TNF-α) and some cell surface glycosylated protein involved in antigen present (MHC-I/II), cell adhesion and migration (chemokine MCP-1 and receptor CCR2; LFA-1, ICAM-1) were upregulated in B4GALT5 overexpressed PRRSV infected cells. Our results demonstrated that the regulation of pB4GALT5 plays an important roles in PRRSV proliferation and modification function in viral infection cells. And these results will make achievements by supporting the research of latent mechanisms of β-1, 4 galactosyltransferase V in antiviral immunity.

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Porcine reproductive and respiratory syndrome virus (PRRSV) induces IL-12p40 production through JNK-AP-1 and NF-κB signaling pathways

Cited by 17 publications

References 55 publications

The Nucleocapsid Protein and Nonstructural Protein 10 of Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Enhance CD83 Production via NF-κB and Sp1 Signaling Pathways

The Nucleocapsid Protein and Nonstructural Protein 10 of Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Enhance CD83 Production via NF-κB and Sp1 Signaling Pathways

A Novel lncRNA Regulates the Toll-Like Receptor Signaling Pathway and Related Immune Function by Stabilizing FOS mRNA as a Competitive Endogenous RNA

The Immunological Regulation Roles of Porcine β-1, 4 Galactosyltransferase V (B4GALT5) in PRRSV Infection

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