Identification of lncRNA-155 encoded by MIR155HG as a novel regulator of innate immunity against influenza A virus infection.
Long noncoding RNAs (lncRNAs) are single-stranded RNA molecules longer than 200 nt that regulate many cellular processes. MicroRNA 155 host gene (MIR155HG) encodes the microRNA (miR)-155 that regulates various signalling pathways of innate and adaptive immune responses against viral infections. MIR155HG also encodes a lncRNA that we call lncRNA-155. Here, we observed that expression of lncRNA-155 was markedly upregulated during influenza A virus (IAV) infection both in vitro (several cell lines) and in vivo (mouse model). Interestingly, robust expression of lncRNA-155 was also induced by infections with several other viruses. Disruption of lncRNA-155 expression in A549 cells diminished the antiviral innate immunity against IAV. Furthermore, knockout of lncRNA-155 in mice significantly increased IAV replication and virulence in the animals. In contrast, overexpression of lncRNA-155 in human cells suppressed IAV replication, suggesting that lncRNA-155 is involved in host antiviral innate immunity induced by IAV infection. Moreover, we found that lncRNA-155 had a profound effect on expression of protein tyrosine phosphatase 1B (PTP1B) during the infection with IAV. Inhibition of PTP1B by lncRNA-155 resulted in higher production of interferon-beta (IFN-β) and several critical interferon-stimulated genes (ISGs). Together, these observations reveal that MIR155HG derived lncRNA-155 can be induced by IAV, which modulates host innate immunity during the virus infection via regulation of PTP1B-mediated interferon response.
['Maarouf|Mohamed|M|0000-0002-1762-5387', 'Chen|Biao|B|', 'Chen|Yuhai|Y|', 'Wang|Xuefei|X|', 'Rai|Kul Raj|KR|', 'Zhao|Zhonghui|Z|', 'Liu|Shasha|S|', 'Li|Yingying|Y|', 'Xiao|Meng|M|', 'Chen|Ji-Long|JL|0000-0002-4274-0563']
D000072283:A549 Cells D000818:Animals D016207:Cytokines D005786:Gene Expression Regulation D057809:HEK293 Cells D054884:Host-Pathogen Interactions D006801:Humans D007113:Immunity, Innate D009980:Influenza A virus D007251:Influenza, Human D000072640:Interferon-Induced Helicase, IFIH1 D016899:Interferon-beta D007371:Interferon-gamma D051379:Mice D035683:MicroRNAs D016328:NF-kappa B D041681:NIH 3T3 Cells D009843:Oligoribonucleotides D009976:Orthomyxoviridae Infections D000067996:RAW 264.7 Cells D062085:RNA, Long Noncoding D015398:Signal Transduction D016019:Survival Analysis D051196:Toll-Like Receptor 3 D014452:Ubiquitins D014779:Virus Replication
MIR155HG innate immunity influenza A virus lncRNA PTP1B miR-155