A novel lncRNA DFRV plays a dual function in influenza A virus infection

Keyu Wang; Meiliang Gong; Sumin Zhao; Chengcai Lai; Lingna Zhao; Sijie Cheng; Min Xia; Yuru Li; Kun Wang; Heqiang Sun; Pingjun Zhu; Yu Zhou; Qiangguo Ao; Xinli Deng

doi:10.3389/fmicb.2023.1171423

A novel lncRNA DFRV plays a dual function in influenza A virus infection

Front Microbiol. 2023 May 25:14:1171423. doi: 10.3389/fmicb.2023.1171423. eCollection 2023.

Authors

Keyu Wang¹, Meiliang Gong¹, Sumin Zhao², Chengcai Lai³, Lingna Zhao⁴, Sijie Cheng⁵, Min Xia⁶, Yuru Li¹, Kun Wang¹, Heqiang Sun¹, Pingjun Zhu⁷, Yu Zhou¹, Qiangguo Ao⁸, Xinli Deng¹

Affiliations

¹ Department of Clinical Laboratory, National Clinical Research Center for Geriatric Diseases, The Second Medical Center of Chinese PLA General Hospital, Beijing, China.
² The PLA Rocket Force Characteristic Medical Center, Beijing, China.
³ Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, China.
⁴ Beijing Key Laboratory for Immunological Research on Chronic Diseases, School of Medicine and Institute for Immunology, Tsinghua University, Beijing, China.
⁵ Center for Disease Prevention and Control, Changde, Hunan, China.
⁶ Department of Vascular Cell Biology, Max Plank Institute for Molecular Biomedicine, Münster, Germany.
⁷ Department of Respiratory and Critical Care Medicine, National Clinical Research Center for Geriatric Diseases, The Second Medical Center of Chinese PLA General Hospital, Beijing, China.
⁸ Department of Nephrology, National Clinical Research Center for Geriatric Diseases, The Second Medical Center of Chinese PLA General Hospital, Beijing, China.

Abstract

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.

Keywords: influenza A virus; innate immune; long noncoding RNA; proinflammatory signaling; viral replication.