title: Porcine circovirus type 2 induces type I interferon production via MyD88-IKKα-IRFs signaling rather than NF-κB in porcine alveolar macrophages in vitro.
abstract: Type I interferon (IFN-I) plays important roles in host antiviral responses. The interferon regulatory factor (IRF) and NF-κB transcription factors are thought to be important in the processes of viral secretion and triggering of interferon production. Recently, studies have shown that porcine circovirus type 2 (PCV2) can induce IFN-I production in vivo and in vitro, but the mechanisms underlying the production of PAMs infected with PCV2 remains unknown. Treatment of these cells with BAY11-7082, an inhibitor of NF-κB activation, allowed us to study the secretion of IFN-α and IFN-β in PAMs infected with PCV2. We found that IFN-α expression was induced following virus infection of PAMs. Notably, even after inhibitor treatment of PAMs infected with PCV2, secretion of IFN-α was significantly higher (P<0.05) compared with the PCV2 infection alone group. Our findings suggest that NF-κB plays a minor role in PCV2-induced type I interferon responses. To further characterize the signaling pathway that drives IFN-I expression in PAMs in response to PCV2, we used siRNA to silence the expression of Myeloid differentiation factor 88 (MyD88) and study the role of MyD88-IKKα-IRF signaling in IFN-I production in PAMs induced by PCV2. Our findings show that PCV2 induced IFN-α mRNA transcription, which is associated with the activities of MyD88, IRF7, and IRF3. Thus, PCV2 can induce IFN-I transcription via the MyD88-IKKα-IRF signaling axis.
authors: College of Veterinary Medicine, Nanjing Agricultural University, Weigang 1, Nanjing 210095, China.
authors: Mengmeng
authors: M
authors: Chen
authors: College of Veterinary Medicine, Nanjing Agricultural University, Weigang 1, Nanjing 210095, China.
authors: Junyuan
authors: J
authors: Han
authors: College of Veterinary Medicine, Nanjing Agricultural University, Weigang 1, Nanjing 210095, China.
authors: Yaqun
authors: Y
authors: Zhang
authors: College of Veterinary Medicine, Nanjing Agricultural University, Weigang 1, Nanjing 210095, China.
authors: Dianning
authors: D
authors: Duan
authors: College of Veterinary Medicine, Nanjing Agricultural University, Weigang 1, Nanjing 210095, China. Electronic address: shuxia@njau.edu.cn.
authors: Shuxia
authors: S
authors: Zhang
mesh_terms: D000818:Animals; D018173:Circoviridae Infections / Q000276:immunology / Q000662:veterinary* / Q000821:virology; D017925:Circovirus / Q000502:physiology*; D016679:Genome, Viral; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000378:metabolism; D007370:Interferon Type I / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000276:immunology; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D015398:Signal Transduction; D013552:Swine; D013553:Swine Diseases / Q000276:immunology* / Q000821:virology
chemical_list: D050835:Interferon Regulatory Factors; D007370:Interferon Type I; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D051550:I-kappa B Kinase
keywords: Porcine alveolar macrophages; Porcine circovirus type 2; Signaling pathway; Type I interferon