MIR155HG Plays a Bivalent Role in Regulating Innate Antiviral Immunity by Encoding Long Noncoding RNA-155 and microRNA-155-5p
Kul Raj Rai, Yuan Liao, Mengjuan Cai, Haori Qiu, Faxin Wen, Min Peng, Song Wang, Shasha Liu, Guijie Guo, Xiaojuan Chi, Mohamed Maarouf, Yongqin David Chen, Shile Huang, Ji‐Long Chen
Abstract
Here, we found that lncRNA-155KO mice lacking most of the lncRNA-155 sequences along with pre-miRNA-155, were more susceptible to influenza virus or pseudorabies virus infection than miRNA-155KO mice lacking only 19 bp of the miRNA-155 core sequence without affecting the expression of lncRNA-155, as evidenced by faster body weight loss, poorer survival, and higher viral load, suggesting an additional role of lncRNA-155 in regulating viral pathogenesis besides via processing miRNA-155. Congruously, miRNA-155-deleted lncRNA-155 significantly attenuated the viral infection. Mechanistically, we demonstrated miRNA-155-5p potentiated antiviral responses by promoting STAT1 activation but could not directly regulate the IFN-β expression. In contrast, lncRNA-155 enhanced virus-induced IFN-β production by regulating the activation of interferon regulatory factor 3. This finding reveals a bivalent role of MIR155HG in regulating antiviral responses through encoding lncRNA-155 and miRNA-155-5p and provides new insights into complicated mechanisms underlying interaction between virus and host innate immunity.