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Downregulation of miR-296-3p by highly pathogenic porcine reproductive and respiratory syndrome virus activates the IRF1/TNF-α signaling axis in porcine alveolar macrophages

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Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV, species Betaarterivirus suid 1 or 2) is a major pathogen affecting pigs on farms throughout the world. miR-296-3p is a multifunctional microRNA involved in the regulation of the inflammatory response in mice and humans. However, little is known about the biological functions of miR-296-3p in pigs. In this study, we used a highly pathogenic PRRSV-2 (species Betaarterivirus suid 2) strain to show that PRRSV infection robustly downregulates the expression of miR-296-3p in porcine alveolar macrophages (PAMs). Furthermore, we demonstrated that overexpression of miR-296-3p increases the replication of highly pathogenic (HP)-PRRSV in PAMs. Notably, the overexpression of miR-296-3p inhibited the induction of TNF-α, even with increased viral replication, compared with that in the HP-PRRSV-infected control group. We also demonstrated that miR-296-3p targets IRF1-facilitated viral infection and modulates the expression of TNF-α in PAMs during HP-PRRSV infection and that IRF1 regulates the expression of TNF-α by activating the TNF promoter via IRF1 response elements. In summary, these findings show that HP-PRRSV infection activates the IRF1/TNF-α signaling axis in PAMs by downregulating host miR-296-3p. This extends our understanding of the inflammatory response induced by HP-PRRSV infection.

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Acknowledgements

This study was supported, in part, by the National Natural Science Foundation of China (31972693), the National Key R&D Program of China (2018YFD0500101), the Chinese Special Fund for Agro-Scientific Research in the Public Interest (no. 2020JB04), and the Elite Program of CAAS (to YQ).

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Authors and Affiliations

  1. Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), 518 Ziyue Road, Shanghai, 200241, China

    Yanbing Zhang, Xiao Xiang, Yan Lu, Hui Li, Abdul Wahaab, Mona Sharma, Ke Liu, Jianchao Wei, Zongjie Li, Donghua Shao, Beibei Li, Zhiyong Ma & Yafeng Qiu

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  1. Yanbing Zhang
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Contributions

YQ conceived and designed the experiments; YZ performed the experiments; XX, YL, HL, AW, MS, KL, JW, ZL, DS, and BL contributed to the preparation of samples and reagents/materials; YZ, ZM, and YQ wrote the paper. All of the authors approved the final manuscript.

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Correspondence to Zhiyong Ma or Yafeng Qiu.

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Zhang, Y., Xiang, X., Lu, Y. et al. Downregulation of miR-296-3p by highly pathogenic porcine reproductive and respiratory syndrome virus activates the IRF1/TNF-α signaling axis in porcine alveolar macrophages. Arch Virol 166, 511–519 (2021). https://doi.org/10.1007/s00705-020-04921-y

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