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Production of porcine TNFα by ADAM17-mediated cleavage negatively regulates porcine reproductive and respiratory syndrome virus infection

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Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) causes a series of inflammatory reactions in sites of infection, companied by the upregulation of key inflammatory factor TNFα. TNFα, which serves as a “master regulator” of inflammatory cytokine production, is mainly produced by macrophages at the early infection stage. Here, we showed that porcine alveolar macrophages produced a great amount of soluble TNFα upon PRRSV infection. Furthermore, we found that TNFα had great anti-PRRSV effect. Next, by using inhibitor and genetic modification methods, we addressed that porcine TNFα production was mediated by ADAM17. Lastly, we proved that the 78Arg–Ser–Ser motif of porcine TNFα contained the essential information for efficient cleavage. Taken together, our findings provide the direct evidence that ADAM17 cleaves porcine TNFα, which represents a new view for identifying potential therapeutic targets in anti-PRRSV therapy.

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Acknowledgments

The research was supported by National Natural Science Foundation of China (31372416).

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  1. State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, China

    Ren Li, Longjun Guo, Weihong Gu, Xiaolei Luo, Jian Zhang, Yunfei Xu, Zhijun Tian, Li Feng & Yue Wang

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  1. Ren Li
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Correspondence to Yue Wang.

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Li, R., Guo, L., Gu, W. et al. Production of porcine TNFα by ADAM17-mediated cleavage negatively regulates porcine reproductive and respiratory syndrome virus infection. Immunol Res 64, 711–720 (2016). https://doi.org/10.1007/s12026-015-8772-8

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