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MicroRNA-30a-5p promotes replication of porcine circovirus type 2 through enhancing autophagy by targeting 14-3-3

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Abstract

Accumulating evidence demonstrates that autophagy and microRNAs (miRNAs) play key roles in regulating virus-host interactions and can restrict or facilitate viral replication. In the present study we examined whether a functional relationship exists between autophagy, miRNA and porcine circovirus type 2 (PCV2) infection, using several approaches. We demonstrated that there was a positive correlation between PCV2 infection and autophagy in 3D4/21 cells and autophagy induced by PCV2 infection triggered PCV2 replication. Four miRNA were selected by real-time PCR and further studied, but only miR-30a-5p mimic had a significant effect on PCV2 replication. Overexpression of miR-30a-5p significantly enhanced PCV2 infection and autophagy in a dose-dependent manner. Blockage of miR-30a-5p significantly decreased PCV2 replication. We provided further evidence that miR-30a-5p regulate the link between PCV2 infection and host immune system. Furthermore, miR-30a-5p targeted and regulated 14-3-3 gene, which is a regulator of autophagy. Flow cytometry data demonstrated that miR-30a-5p promotes cell cycle arrest at the G2 phase to regulate PCV2 replication and autophagy by interacting directly with 14-3-3, but not with the PCV2 genome. These data not only provide new insights into virus-host interactions during PCV2 infection but also suggest a potential new antiviral therapeutic strategy against PCV2 infection.

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Correspondence to Kongwang He or Hongjie Fan.

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This study was funded by the National Natural Science Foundation of China (31302071), Independent Innovation of Agricultural Sciences in Jiangsu province (CX (14)5041) and Special Fund for Public Welfare Industry of Chinese Ministry of Agriculture (201303046).

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Wang, X., Xu, X., Wang, W. et al. MicroRNA-30a-5p promotes replication of porcine circovirus type 2 through enhancing autophagy by targeting 14-3-3. Arch Virol 162, 2643–2654 (2017). https://doi.org/10.1007/s00705-017-3400-7

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