Identification of an Interferon-Stimulated Long Noncoding RNA (LncRNA ISR) Involved in Regulation of Influenza A Virus Replication

Abstract

Long noncoding RNAs (lncRNAs) are involved in a diversity of biological processes. It is known that differential expression of thousands of lncRNAs occurs in host during influenza A virus (IAV) infection. However, only few of them have been well characterized. Here, we identified a lncRNA, named as interferon (IFN)-stimulated lncRNA (ISR), which can be significantly upregulated in response to IAV infection in a mouse model. A sequence alignment revealed that lncRNA ISR is present in mice and human beings, and indeed, we found that it was expressed in several human and mouse cell lines and tissues. Silencing lncRNA ISR in A549 cells resulted in a significant increase in IAV replication, whereas ectopic expression of lncRNA ISR reduced the viral replication. Interestingly, interferon-β (IFN-β) treatment was able to induce lncRNA ISR expression, and induction of lncRNA ISR by viral infection was nearly abolished in host deficient of IFNAR1, a type I IFN receptor. Furthermore, the level of IAV-induced lncRNA ISR expression was decreased either in retinoic acid-inducible gene I (RIG-I) knockout A549 cells and mice or by nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) inhibitor treatment. Together, these data elucidate that lncRNA ISR is regulated by RIG-I-dependent signaling that governs IFN-β production during IAV infection, and has an inhibitory capacity in viral replication.

In silico analysis of altered expression of long non-coding RNA in SARS-CoV-2 infected cells and their possible regulation by STAT1, STAT3 and interferon regulatory factors

“…Infections with influenza virus (IAV), HIV, herpes simplex virus (HSV), hepatitis C virus (HCV), hepatitis B virus (HBV), severe acute respiratory syndrome coronavirus (SARS-CoV) and others alter the expression of host lncRNA 19 , 20 . Expression of lncRNA EGOT, NEAT1, BISPR/LncBST2, LINC01191/VIN/lnc-ACTR3, ISR (IFN-stimulated lncRNA) 2 and ISR8, LOC100506319/LINC01988/LncRNA-PAAN, LOC102637961/lncRNA-ACOD1, MIR155HG, TSPOAP1-AS1, PSMB8-AS1, PSORS1C3, IVRPIE was increased and expression of NRAV/DYNLL1AS1 was decreased in IAV infected cells 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 . In HIV infected cells expression of ISR2, NEAT1, GOMAFU/MIAT, LUST/RBM5-AS1, BIC/MIR155HG, MALAT1, NRIR/lncCMPK2, MIR3945HG, FIRRE, LINC02574, LINC01426 is increased while expression of NRON, PANDAR/PANDA, CDKN2B-AS1/ANRIL DD3/PCA, DANCR, CMPD/LINC01152, NCRMS/RMST, GAS5, LINC00173, lincRNA-p21/TP53COR1 and SAF/FAS-AS1 is decreased 29 , 30 , 31 .…”

Zinc Finger CCCH-Type Antiviral Protein 1 Restricts the Viral Replication by Positively Regulating Type I Interferon Response

“…Plaque assay was performed to quantify the viral replication in A549 cells as described previously (Qidong et al, 2019). Briefly, supernatants from A549 cells infected with influenza A/WSN/33 (WSN) virus were collected.…”

Roles of lncRNAs in influenza virus infection

“…lnc-ISG20 acts as a competitive endogenous RNA (ceRNA), binds miR-326 to reduce its inhibition of ISG20 translation [22]. In addition, lncRNA ISR is also induced by IAV infection and by IFN-β, thus functions as an ISG to inhibit IAV replication [59].…”