Long noncoding RNA AVAN promotes antiviral innate immunity by interacting with TRIM25 and enhancing the transcription of FOXO3a

Chengcai Lai; Lihui Liu; Qinghua Liu; Sijie Cheng; Keyu Wang; Lingna Zhao; Min Xia; Cheng Wang; Hongjing Gu; Yueqiang Duan; Zhongpeng Zhao; Lili Zhang; Ziyang Liu; Jianjun Luo; Jianxun Song; Penghui Yang; Runsheng Chen; Xiliang Wang

The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. . https://doi.org/10.1101/623132 doi: bioRxiv preprint used for RNA pull-down assay. The result indicated that the TRIM25-binding activity mapped 262 between nucleotides 1 and 200 ( Fig 6G) . Together, these findings indicate that AVAN The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. . https://doi.org/10.1101/623132 doi: bioRxiv preprint addition, AVAN overexpression increased TBK1 and IRF3 phosphorylation upon IAV-BJ501 284 infection (Fig S7E, left) . In contrast, AVAN knockdown abolished these changes (Fig S7E, 285 right). To test whether AVAN enhances the IFN-mediated antiviral innate immune response 286 through TRIM25 and RIG-I signaling, we performed qPCR analysis measuring 287 IFN-alpha/beta upon AVAN transfection, and then individually knock down RIG-I or TRIM25. 288 The results showed that knock down RIG-I or TRIM25 abrogated AVAN-induced effects on 289 IFN-alpha/beta expression during IAV-BJ501 infection (Fig 6M, N, Fig S7F, G) . Together, 290 these data show that AVAN can enhance the interaction between TRIM25 and RIG-I and the 291 ubiquitylation of RIG-I in the cytoplasm. Thus, we conclude that AVAN promotes TRIM25-292 and RIG-I-mediated antiviral innate immune signaling. transgenic mice (TG) mice expressing human AVAN were generated as previously 298 described (52) . TG mice lung with high AVAN expression were identified and selected for this 299 experiment ( Fig 7A) . TG mice and WT littermates were i.n. inoculated with BJ501 virus. As 300 expected, IAV-BJ501 displayed a considerably lower virulence in TG mice than that in WT 301 mice. The survival rates were 60% and 20% in TG mice and WT mice after 14 days 302 post-infection, respectively (Fig 7B) . The TG mice exhibited significantly reduced body 303 weight loss at 7 days post-infection compared with the WT mice ( Fig 7C) . Meanwhile, we 304 compared the lung edema and viral loads of infected TG mice with WT littermates and found 305 All rights reserved. No reuse allowed without permission.