4.7 Article

Porcine circovirus type 2 infection inhibits the activation of type I interferon signaling via capsid protein and host gC1qR

期刊

VETERINARY MICROBIOLOGY
卷 266, 期 -, 页码 -

出版社

ELSEVIER
DOI: 10.1016/j.vetmic.2022.109354

关键词

Porcine circovirus type 2 (PCV2); Type I interferon signaling; JAK -STAT pathway; Capsid; gC1qR

资金

  1. National Natural Science Foundation of China [31972686, 31872447]
  2. Key RAMP
  3. D Program of Shaanxi Province [2018ZDCXL-NY-02-07, 2020NY-010]
  4. Fundamental Research Funds for the Central Universities [2452017023]

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PCV2 infection interferes with the activation of type I interferon signaling pathway through its Cap protein and host gC1qR protein, resulting in reduced transcription of IFN-stimulated genes.
Porcine circovirus 2 (PCV2) has been proved to increase the risk of other pathogens infection through antagonizing the host type I interferon (IFN) response. Previously, we have reported that PCV2 infection efficiently inhibits type I interferon production induced by other DNA viruses. However, whether PCV2 can inhibit type I interferon signaling is less reported. Herein, we found that PCV2 interfered with the activation of IFN signaling pathway, which led to a significantly reduced IFN-stimulated genes (ISGs) transcription after IFN-alpha stimulation both in vivo and in vitro. In PCV2-infected cells, IFN-induced tyrosine phosphorylation of STAT1 and STAT2 and their heterodimerization were decreased. Meanwhile, the nuclear translocation of phosphorylated STAT1/STAT2 was also decreased. Based on these findings, we further determined that roles of PCV2 Cap and Rep in the suppression of IFN-I signaling, and found that Cap acted as a predominant regulator in the early phase infection. PCV2 Cap could significantly reduce the phosphorylation of STAT1 and STAT2, the nuclear translocation of phosphorylated STAT1/STAT2, and IFN-stimulated response element (ISRE) promoter activity, results in a decreased ISGs transcription. As the binding protein of PCV2 Cap, gC1qR protein was also involved in this inhibition process. Knockdown of gC1qR could alleviate the inhibitory effects of either PCV2 infection or Cap on the activation of IFN signaling. These findings demonstrated that PCV2 infection interferes with the activation of type I IFNs signaling pathway depending on its Cap and host gC1qR protein.

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