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Open AccessArticle

PP2A Facilitates Porcine Reproductive and Respiratory Syndrome Virus Replication by Deactivating irf3 and Limiting Type I Interferon Production

1
State Key Laboratory of Veterinary Biotechnology, Heilongjiang Provincial Key Laboratory of Laboratory Animal and Comparative Medicine, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China
2
Department of public health policy, University of California, Irvine, CA 92697, USA
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this study.
Viruses 2019, 11(10), 948; https://doi.org/10.3390/v11100948
Received: 28 August 2019 / Revised: 11 October 2019 / Accepted: 11 October 2019 / Published: 15 October 2019
(This article belongs to the Special Issue Porcine Viruses 2019)
Protein phosphatase 2A (PP2A), a major serine/threonine phosphatase in mammalian cells, is known to regulate the kinase-driven intracellular signaling pathways. Emerging evidences have shown that the PP2A phosphatase functions as a bona-fide therapeutic target for anticancer therapy, but it is unclear whether PP2A affects a porcine reproductive and respiratory syndrome virus infection. In the present study, we demonstrated for the first time that inhibition of PP2A activity by either inhibitor or small interfering RNA duplexes in target cells significantly reduced their susceptibility to porcine reproductive and respiratory syndrome virus (PRRSV) infection. Further analysis revealed that inhibition of PP2A function resulted in augmented production of type I interferon (IFN). The mechanism is that inhibition of PP2A activity enhances the levels of phosphorylated interferon regulatory factor 3, which activates the transcription of IFN-stimulated genes. Moreover, inhibition of PP2A activity mainly blocked PRRSV replication in the early stage of viral life cycle, after virus entry but before virus release. Using type I IFN receptor 2 specific siRNA in combination with PP2A inhibitor, we confirmed that the effect of PP2A on viral replication within target cells was an interferon-dependent manner. Taken together, these findings demonstrate that PP2A serves as a negative regulator of host cells antiviral responses and provides a novel therapeutic target for virus infection. View Full-Text
Keywords: PRRSV; PP2A; type I interferon; IRF3; antiviral response PRRSV; PP2A; type I interferon; IRF3; antiviral response
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MDPI and ACS Style

Xu, J.; Zhang, L.; Xu, Y.; Zhang, H.; Gao, J.; Wang, Q.; Tian, Z.; Xuan, L.; Chen, H.; Wang, Y. PP2A Facilitates Porcine Reproductive and Respiratory Syndrome Virus Replication by Deactivating irf3 and Limiting Type I Interferon Production. Viruses 2019, 11, 948. https://doi.org/10.3390/v11100948

AMA Style

Xu J, Zhang L, Xu Y, Zhang H, Gao J, Wang Q, Tian Z, Xuan L, Chen H, Wang Y. PP2A Facilitates Porcine Reproductive and Respiratory Syndrome Virus Replication by Deactivating irf3 and Limiting Type I Interferon Production. Viruses. 2019; 11(10):948. https://doi.org/10.3390/v11100948

Chicago/Turabian Style

Xu, Jiayu; Zhang, Lu; Xu, Yunfei; Zhang, He; Gao, Junxin; Wang, Qian; Tian, Zhijun; Xuan, Lv; Chen, Hongyan; Wang, Yue. 2019. "PP2A Facilitates Porcine Reproductive and Respiratory Syndrome Virus Replication by Deactivating irf3 and Limiting Type I Interferon Production" Viruses 11, no. 10: 948. https://doi.org/10.3390/v11100948

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