Wang Keyu, Gong Meiliang, Zhao Sumin, Lai Chengcai, Zhao Lingna, Cheng Sijie, Xia Min, Li Yuru, Wang Kun, Sun Heqiang, Zhu Pingjun, Zhou Yu, Ao Qiangguo, Deng Xinli
Department of Clinical Laboratory, National Clinical Research Center for Geriatric Diseases, The Second Medical Center of Chinese PLA General Hospital, Beijing, China.
The PLA Rocket Force Characteristic Medical Center, Beijing, China.
Front Microbiol. 2023 May 25;14:1171423. doi: 10.3389/fmicb.2023.1171423. eCollection 2023.
Long noncoding RNAs (lncRNAs) have been associated with a variety of biological activities, including immune responses. However, the function of lncRNAs in antiviral innate immune responses are not fully understood. Here, we identified a novel lncRNA, termed dual function regulating influenza virus (DFRV), elevating in a dose- and time-dependent manner during influenza A virus (IAV) infection, which was dependent on the NFκB signaling pathway. Meanwhile, DFRV was spliced into two transcripts post IAV infection, in which DFRV long suppress the viral replication while DFRV short plays the opposite role. Moreover, DFRV regulates IL-1β and TNF-α via activating several pro-inflammatory signaling cascades, including NFκB, STAT3, PI3K, AKT, ERK1/2 and p38. Besides, DFRV short can inhibit DFRV long expression in a dose-dependent manner. Collectively, our studies reveal that DFRV may act as a potential dual-regulator to preserve innate immune homeostasis in IAV infection.
长链非编码RNA(lncRNAs)与多种生物学活性相关,包括免疫反应。然而,lncRNAs在抗病毒天然免疫反应中的功能尚未完全明确。在此,我们鉴定出一种新型lncRNA,命名为双功能调节流感病毒(DFRV),在甲型流感病毒(IAV)感染期间呈剂量和时间依赖性升高,这依赖于NFκB信号通路。同时,IAV感染后DFRV被剪接成两种转录本,其中DFRV长转录本抑制病毒复制,而DFRV短转录本则起相反作用。此外,DFRV通过激活包括NFκB、STAT3、PI3K、AKT、ERK1/2和p38在内的多种促炎信号级联反应来调节IL-1β和TNF-α。此外,DFRV短转录本可以剂量依赖性方式抑制DFRV长转录本的表达。总体而言,我们的研究表明DFRV可能作为一种潜在的双调节因子,在IAV感染中维持天然免疫稳态。