Long noncoding RNA 1392 regulates MDA5 by interaction with ELAVL1 to inhibit coxsackievirus B5 infection  

作　　者：Jing Li Jinwei Li Peiying Teng Fan Yang Jihong Zhang Bo Sun Wei Chen 

机构地区：[1]Medical School,Kunming University of Science and Technology,Kunming,650500,China

出　　处：《Virologica Sinica》2023年第5期699-708,共10页中国病毒学（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(No.81860357);the Young Talents Support Program of Yunnan Province,China(Ten Thousand People Plan,YNWR-QNBJ-2019-178).

摘　　要：Long noncoding RNAs(lncRNAs)modulate many aspects of biological and pathological processes.Recent studies have shown that host lncRNAs participate in the antiviral immune response,but functional lncRNAs in coxsackievirus B5(CVB5)infection remain unknown.Here,we identified a novel cytoplasmic lncRNA,LINC1392,which was highly inducible in CVB5 infected RD cells in a time-and dose-dependent manner,and also can be induced by the viral RNA and IFN-β.Further investigation showed that LINC1392 promoted several important interferon-stimulated genes(ISGs)expression,including IFIT1,IFIT2,and IFITM3 by activating MDA5,thereby inhibiting the replication of CVB5 in vitro.Mechanistically,LINC1392 bound to ELAV like RNA binding protein 1(ELAVL1)and blocked ELAVL1 interaction with MDA5.Functional study revealed that the 245–835 nt locus of LINC1392 exerted the antiviral effect and was also an important site for ELAVL1 binding.In mice,LINC1392 could inhibit CVB5 replication and alleviated the histopathological lesions of intestinal and brain tissues induced by viral infection.Our findings collectively reveal that the novel LINC1392 acts as a positive regulator in the IFN-I signaling pathway against CVB5 infection.Elucidating the underlying mechanisms on how lncRNA regulats the host innate immunity response towards CVB5 infection will lay the foundation for antiviral drug research.

关 键 词：Long noncoding RNAs(lncRNAs) Coxsackievirus B5(CVB5) Type I interferon(IFN-I)signaling pathway Melanoma differentiation-associated gene 5 (MDA5) ELAV like RNA binding protein 1(ELAVL1) 

分 类 号：R373.21[医药卫生—病原生物学]