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MCPIP1 inhibits coxsackievirus B3 replication by targeting viral RNA and negatively regulates virus-induced inflammation

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Abstract

Monocyte chemotactic protein-induced protein 1(MCPIP1) is identified as an important inflammatory regulator during immune response. MCPIP1 possesses antiviral activities against several viruses, such as Japanese encephalitis. However, its role on Coxsackievirus B3 (CVB3) infection, a positive-stranded RNA virus, has not been addressed. Here, we reported that MCPIP1 was up-regulated in cardiomyocytes by CVB3 infection and in hearts and pancreas of infected mice. Then we found that overexpression of MCPIP1 inhibited CVB3 replication and knockdown of it promoted virus replication. Luciferase assay demonstrated MCPIP1 targeting non-ARE region of CVB3 3′UTR, which was dependent on its RNase, RNA binding and oligomerization abilities, but not deubiquitinase activity. We further verified that MCPIP1 negatively regulated CVB3-induced inflammatory response in macrophages. Thus, our data suggest MCPIP1 as a potent host defense against CVB3 infection and viral myocarditis.

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Acknowledgements

This work was supported by Chinese National Natural Science Foundation (31400769, 31670930, 31470869, and 31072973), Jiangsu Province Natural Science Foundation (BK20140371) and Jiangsu Postdoctor Science Foundation (1402176C), Major State Basic Research Development Program of China (2013CB531502), the Natural Science foundation of Jiangsu Province Higher education (14KJA310005), the Jiangsu Provincial Innovative Research Team, Project funded by priority Academic Program Development of Jiangsu Higher Education Institutions, and Program for Changjiang Scholars and Innovative Research Team in University (Grant PCSIRTIRT1075).

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  1. Min Li and Kepeng Yan contributed equally to this work.

Authors and Affiliations

  1. Institute of Biology and Medical Sciences, Soochow University, Building 703, 199 Ren-ai Road, Suzhou, 215123, China

    Min Li, Kepeng Yan, Lin Wei, Yang Yang, Qian Qian & Wei Xu

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  1. Min Li
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  2. Kepeng Yan
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  3. Lin Wei
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Correspondence to Wei Xu.

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Li, M., Yan, K., Wei, L. et al. MCPIP1 inhibits coxsackievirus B3 replication by targeting viral RNA and negatively regulates virus-induced inflammation. Med Microbiol Immunol 207, 27–38 (2018). https://doi.org/10.1007/s00430-017-0523-0

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