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Porcine Circovirus Type 2 Rep Enhances IL-10 Production in Macrophages via Activation of p38-MAPK Pathway

College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China
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Authors to whom correspondence should be addressed.
These authors contribute equally to this work.
Viruses 2019, 11(12), 1141; https://doi.org/10.3390/v11121141
Received: 2 October 2019 / Revised: 6 December 2019 / Accepted: 8 December 2019 / Published: 10 December 2019
(This article belongs to the Section Animal Viruses)
Porcine circovirus type 2 (PCV2) is one of the major threats to pig farms worldwide. Although PCV2 has been identified to promote IL-10 production, the detailed regulatory roles of PCV2 Rep for IL-10 production remain unclear. Herein, we first found that PCV2 Rep, rather than PCV1 Rep, enhanced IL-10 expression at the later phase of PCV2 infection in porcine alveolar macrophages (PAMs). Furthermore, we found that PCV2 Rep directly activated the p38-MAPK pathway to promote transcription factors NF-κB p50 and Sp1 binding to the il10 promoter, but PCV1 Rep did not. During PCV2 infection, however, PCV2 Rep promoted the binding activities of NF-κB p50 and Sp1 with the il10 promoter only at the later phase of PCV2 infection, since Rep proteins only expressed at the later phase of the infection. Moreover, silence of the thymine DNA glycosylase (TDG), a Rep-binding protein, significantly reduced the binding activities of NF-κB p50 and Sp1 with il10 promoter, resulting in the reduction of IL-10 production in PCV2-inoculated PAMs at the later phase of infection. Taken together, our results demonstrate that Rep proteins enhance IL-10 production during PCV2 infection of PAMs via activation of p38-MAPK pathways, in which host TDG is a critical mediator. View Full-Text
Keywords: porcine circovirus type 2 (PCV2); interleukin-10 (IL-10); Rep; p38-MAPK pathway; thymine DNA glycosylase (TDG) porcine circovirus type 2 (PCV2); interleukin-10 (IL-10); Rep; p38-MAPK pathway; thymine DNA glycosylase (TDG)
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Wu, X.; Wang, X.; Shi, T.; Luo, L.; Qiao, D.; Wang, Z.; Han, C.; Du, Q.; Tong, D.; Huang, Y. Porcine Circovirus Type 2 Rep Enhances IL-10 Production in Macrophages via Activation of p38-MAPK Pathway. Viruses 2019, 11, 1141.

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