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RIG-1 and MDA-5 signaling pathways contribute to IFN-β production and viral replication in porcine circovirus virus type 2-infected PK-15 cells in vitro.
Vet Microbiol. 2017 Nov; 211:36-42.VM

Abstract

Type I Interferons (IFNs) is known for its antiviral activity; however, it is surprising that in vitro treatment of IFN-α and IFN-γ enhanced the replication of porcine circovirus type 2 (PCV2), indicating a complex relationship between interferon and PCV2. To date, it remains poorly understood how the interferon is produced during PCV2 infection and whether the interferon induced by PCV2 itself can promote viral replication. In this study, PCV2 induced the up-regulation of IFN-β in PK-15 cells, while treatment of PCV2-infected cells with the interferon regulatory factor-3 (IRF3) inhibitor, BX795, decreased the expression of IFN-β, whereas treatment with the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) inhibitor, BAY11-7082, did not. These findings indicate that PCV2 can induce IFN-β production via the IRF3-mediated rather than the NF-κB-mediated signal pathway. Moreover, PCV2 increased the protein expression levels of phosphorylation-IRF3 (p-IRF3), mitochondria antiviral-signaling protein (MAVS), retinoic acid-inducible gene I (RIG-1) and melanoma differentiation-associated protein 5 (MDA-5), and the knockdown of RIG-1 and MDA-5 decreased the expression level of IFN-β in PK-15 cells. Therefore, PCV2 induces IFN-β production via the RIG-1/MDA-5/MAVS/IRF signaling pathway. Furthermore, the PCV2 load and PCV2 infectivity decreased after knockdown of RIG-1 and MDA-5, indicating that RIG-1 and MDA-5 signaling pathways contribute to PCV2 replication. In conclusion, PCV2 induces the production of IFN-β via the RIG-1 and MDA-5 signaling pathways, and the IFN-β produced during PCV2 infection facilitates viral replication. These results will help us further understand the pathogenic mechanisms of PCV2.

Authors+Show Affiliations

College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China.College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China.College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China.College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China.College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China.College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China. Electronic address: lyj@njau.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29102119

Citation

Huang, Bei, et al. "RIG-1 and MDA-5 Signaling Pathways Contribute to IFN-β Production and Viral Replication in Porcine Circovirus Virus Type 2-infected PK-15 Cells in Vitro." Veterinary Microbiology, vol. 211, 2017, pp. 36-42.
Huang B, Li J, Zhang X, et al. RIG-1 and MDA-5 signaling pathways contribute to IFN-β production and viral replication in porcine circovirus virus type 2-infected PK-15 cells in vitro. Vet Microbiol. 2017;211:36-42.
Huang, B., Li, J., Zhang, X., Zhao, Q., Lu, M., & Lv, Y. (2017). RIG-1 and MDA-5 signaling pathways contribute to IFN-β production and viral replication in porcine circovirus virus type 2-infected PK-15 cells in vitro. Veterinary Microbiology, 211, 36-42. https://doi.org/10.1016/j.vetmic.2017.09.022
Huang B, et al. RIG-1 and MDA-5 Signaling Pathways Contribute to IFN-β Production and Viral Replication in Porcine Circovirus Virus Type 2-infected PK-15 Cells in Vitro. Vet Microbiol. 2017;211:36-42. PubMed PMID: 29102119.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - RIG-1 and MDA-5 signaling pathways contribute to IFN-β production and viral replication in porcine circovirus virus type 2-infected PK-15 cells in vitro. AU - Huang,Bei, AU - Li,Jiansheng, AU - Zhang,Xinchen, AU - Zhao,Qiling, AU - Lu,Mingqing, AU - Lv,Yingjun, Y1 - 2017/09/29/ PY - 2017/07/04/received PY - 2017/09/27/revised PY - 2017/09/28/accepted PY - 2017/11/6/entrez PY - 2017/11/6/pubmed PY - 2018/7/3/medline KW - Interferon KW - MDA-5 KW - PCV2 KW - RIG-1 KW - Viral replication SP - 36 EP - 42 JF - Veterinary microbiology JO - Vet. Microbiol. VL - 211 N2 - Type I Interferons (IFNs) is known for its antiviral activity; however, it is surprising that in vitro treatment of IFN-α and IFN-γ enhanced the replication of porcine circovirus type 2 (PCV2), indicating a complex relationship between interferon and PCV2. To date, it remains poorly understood how the interferon is produced during PCV2 infection and whether the interferon induced by PCV2 itself can promote viral replication. In this study, PCV2 induced the up-regulation of IFN-β in PK-15 cells, while treatment of PCV2-infected cells with the interferon regulatory factor-3 (IRF3) inhibitor, BX795, decreased the expression of IFN-β, whereas treatment with the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) inhibitor, BAY11-7082, did not. These findings indicate that PCV2 can induce IFN-β production via the IRF3-mediated rather than the NF-κB-mediated signal pathway. Moreover, PCV2 increased the protein expression levels of phosphorylation-IRF3 (p-IRF3), mitochondria antiviral-signaling protein (MAVS), retinoic acid-inducible gene I (RIG-1) and melanoma differentiation-associated protein 5 (MDA-5), and the knockdown of RIG-1 and MDA-5 decreased the expression level of IFN-β in PK-15 cells. Therefore, PCV2 induces IFN-β production via the RIG-1/MDA-5/MAVS/IRF signaling pathway. Furthermore, the PCV2 load and PCV2 infectivity decreased after knockdown of RIG-1 and MDA-5, indicating that RIG-1 and MDA-5 signaling pathways contribute to PCV2 replication. In conclusion, PCV2 induces the production of IFN-β via the RIG-1 and MDA-5 signaling pathways, and the IFN-β produced during PCV2 infection facilitates viral replication. These results will help us further understand the pathogenic mechanisms of PCV2. SN - 1873-2542 UR - https://www.unboundmedicine.com/medline/citation/29102119/RIG_1_and_MDA_5_signaling_pathways_contribute_to_IFN_β_production_and_viral_replication_in_porcine_circovirus_virus_type_2_infected_PK_15_cells_in_vitro_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-1135(17)30782-4 DB - PRIME DP - Unbound Medicine ER -