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LSM14A inhibits porcine reproductive and respiratory syndrome virus (PRRSV) replication by activating IFN-β signaling pathway in Marc-145

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Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) is considered as a significant contributor to porcine reproductive and respiratory syndrome, one of the most economically important diseases for the pig industry worldwide. Emerging evidence indicates that pattern recognition receptors play key roles in recognizing pathogen-associated molecular patterns. In the present study, we investigated the effects of a novel pattern recognition receptor LSM14A in regulating PRRSV replication. Results in Marc-145 cells and porcine alveolar macrophages (PAMs) indicated that overexpression of porcine LSM14A effectively inhibited the replication of PRRSV, and knockdown of LSM14A by siRNA enhanced the replication of PRRSV. Mechanistically, LSM14A up-regulated the activities of IFN-β and ISRE promoters, enhanced the production of IFN-β, RIG-I, and ISGs, and inhibited the production of the inflammatory cytokines of TNF-α and IL-6 mRNA. Additionally, the expression pattern of LSM14A during the infection of PRRSV in Tongcheng and Large White pigs was suppressed by the PRRSV challenge. Taken together, our results suggest that LSM14A is an important PRR that inhibits PPRSV replication by inducing IFN-β signaling and restraining inflammatory responses. Furthermore, the down-regulation of LSM14A by PRRSV might represent an important mechanism by which PRRSV invades the host. Our study sheds light on the possibility of developing a new strategy to control this disease.

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Acknowledgments

This study was supported by the Major International Cooperation NSFC (31210103917) and the National High Technology Research and Development Program of China (2011AA100304). We thank Professor Shaobo Xiao (Huazhong Agriculture University, Wuhan, China) for generously providing the PRRSV strain WUH3.

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Authors and Affiliations

  1. Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Ministry of Education and College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China

    Zhenhong Li, Jinhua Zhao, Ziyu Qi, Likai Ji, Yueran Zhen & Bang Liu

  2. Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, 27710, USA

    Rui Chen

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  1. Zhenhong Li
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  2. Rui Chen
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  3. Jinhua Zhao
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  7. Bang Liu
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Correspondence to Bang Liu.

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Li, Z., Chen, R., Zhao, J. et al. LSM14A inhibits porcine reproductive and respiratory syndrome virus (PRRSV) replication by activating IFN-β signaling pathway in Marc-145. Mol Cell Biochem 399, 247–256 (2015). https://doi.org/10.1007/s11010-014-2251-8

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