# Long Non-Coding RNAs Can Govern the Antiviral Immune Response Through Interferon-Mediated Mechanisms in Respiratory Tract

**Authors:** Alexey Lozhkov, Alexey Skvortsov, Valeria Kirenskaya, Andrey Vasin

PMC · DOI: 10.3390/v18020231 · Viruses · 2026-02-12

## TL;DR

This paper reviews how long non-coding RNAs influence antiviral immune responses through interferon signaling in the respiratory tract.

## Contribution

It provides a comprehensive overview of lncRNA roles in interferon-mediated immunity and highlights their potential for treating influenza.

## Key findings

- lncRNAs regulate interferon-dependent immune responses and influenza susceptibility.
- lncRNAs are classified into antisense, bidirectional, intronic, and intergenic types.
- Understanding lncRNA functions could lead to new treatments for influenza.

## Abstract

Many long non-coding RNAs (lncRNAs) are able to control interferon-dependent innate immune responses and the susceptibility to influenza infection. These lncRNAs are primarily regulated through the RIG-I/IFN-β/IFNAR1 pathway and can be considered as interferon-stimulated genes with either antiviral or proviral functions. In this review we observe the current knowledge of type I and III interferon signaling regulation and discuss the present data on specific lncRNAs, which are involved in the interferon response. The available data on mechanisms of lncRNA induction and action are summarized. Also, the brief overview of genes coding for lncRNAs involved in interferon expression regulation is presented with a focus on the evolutionary conservation of these regulatory molecules. The lncRNAs belong to various classes: antisense, bidirectional, intronic, or intergenic RNAs. Research of lncRNAs is an extremely promising scientific area. Deeper understanding of lncRNA functions may result in the development of new approaches to influenza infection treatment, as well as advanced understanding of the disease pathogenesis. Further bioinformatic analysis of lncRNAs is required to reveal putative common mechanisms of lncRNA action.

## Linked entities

- **Genes:** RIGI (RNA sensor RIG-I) [NCBI Gene 23586], IFNB1 (interferon beta 1) [NCBI Gene 3456], IFNAR1 (interferon alpha and beta receptor subunit 1) [NCBI Gene 3454]
- **Diseases:** influenza infection (MONDO:0005812)

## Full-text entities

- **Genes:** MIR155 (microRNA 155) [NCBI Gene 406947] {aka MIRN155, miRNA155, mir-155}, Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, histone H4 [NCBI Gene 102641229], Ptpn1 (protein tyrosine phosphatase, non-receptor type 1) [NCBI Gene 19246] {aka PTP-1B, PTP-HA2, PTP1B}, Tlr3 (toll-like receptor 3) [NCBI Gene 142980], MUL1 (mitochondrial E3 ubiquitin protein ligase 1) [NCBI Gene 79594] {aka C1orf166, GIDE, MAPL, MULAN, RNF218}, Cd14 (CD14 antigen) [NCBI Gene 12475], IL10RB (interleukin 10 receptor subunit beta) [NCBI Gene 3588] {aka CDW210B, CRF2-4, CRFB4, D21S58, D21S66, IBD25}, Ifnb1 (interferon beta 1, fibroblast) [NCBI Gene 15977] {aka IFN-beta, IFNB, If1da1, Ifb}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, TXNIP (thioredoxin interacting protein) [NCBI Gene 10628] {aka ARRDC6, EST01027, HHCPA78, THIF, VDUP1}, Stat2 (signal transducer and activator of transcription 2) [NCBI Gene 20847] {aka 1600010G07Rik}, Ikbke (inhibitor of kappaB kinase epsilon) [NCBI Gene 56489] {aka IKK-E, IKK-i, IKKepsilon, Ikki}, Socs1 (suppressor of cytokine signaling 1) [NCBI Gene 12703] {aka Cish1, Cish7, JAB, SOCS-1, SSI-1}, IFNA8 (interferon alpha 8) [NCBI Gene 3445] {aka IFN-alphaB}, IRF1 (interferon regulatory factor 1) [NCBI Gene 3659] {aka IMD117, IRF-1, MAR}, Irf9 (interferon regulatory factor 9) [NCBI Gene 16391] {aka Irf-9, Isgf3g, p48}, Ifih1 (interferon induced with helicase C domain 1) [NCBI Gene 71586] {aka 9130009C22Rik, Helicard, Hlcd, MDA5, RLR-2}, IFNLR1 (interferon lambda receptor 1) [NCBI Gene 163702] {aka CRF2/12, IFNLR, IL-28R1, IL28RA, LICR2}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Irf2 (interferon regulatory factor 2) [NCBI Gene 16363] {aka 9830146E22Rik, Irf-2}, DYNLL1 (dynein light chain LC8-type 1) [NCBI Gene 8655] {aka DLC1, DLC8, DNCL1, DNCLC1, LC8, LC8a}, Rnf135 (ring finger protein 135) [NCBI Gene 71956] {aka 0610037N03Rik, 2410006N06Rik, Riplet, U 2-3-0}, IFITM1 (interferon induced transmembrane protein 1) [NCBI Gene 8519] {aka 9-27, CD225, DSPA2a, IFI17, LEU13}, Ifit1 (interferon-induced protein with tetratricopeptide repeats 1) [NCBI Gene 15957] {aka GARG-16, IFI-56K, ISG56, Ifi56, P56}, TYK2 (tyrosine kinase 2) [NCBI Gene 7297] {aka IMD35, JTK1}, Mir744 (microRNA 744) [NCBI Gene 791070] {aka Mirn744, mir-744, mmu-mir-744}, Tjp1 (tight junction protein 1) [NCBI Gene 21872] {aka ZO1}, TANK (TRAF family member associated NFKB activator) [NCBI Gene 10010] {aka I-TRAF, ITRAF, TRAF2}, TFAP2A (transcription factor AP-2 alpha) [NCBI Gene 7020] {aka AP-2, AP-2alpha, AP2TF, BOFS, TFAP2}, Rsad2 (radical S-adenosyl methionine domain containing 2) [NCBI Gene 58185] {aka 2510004L01Rik, SAND, Vig1, cig5}, USP30 (ubiquitin specific peptidase 30) [NCBI Gene 84749], IFNAR1 (interferon alpha and beta receptor subunit 1) [NCBI Gene 3454] {aka AVP, CRF2-1, IFN-R-1, IFN-alpha-REC, IFNAR, IFNBR}, Trim25 (tripartite motif-containing 25) [NCBI Gene 217069] {aka EFP, Zfp147}, Oasl2 (2'-5' oligoadenylate synthetase-like 2) [NCBI Gene 23962] {aka M1204, Mmu-OASL, Oasl}, Ccl5 (C-C motif chemokine ligand 5) [NCBI Gene 20304] {aka MuRantes, RANTES, SISd, Scya5, TCP228}, IFNGR2 (interferon gamma receptor 2) [NCBI Gene 3460] {aka AF-1, IFGR2, IFNGT1, IMD28}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, Ifnar1 (interferon (alpha and beta) receptor 1) [NCBI Gene 15975] {aka Ifar, Ifnar, Ifrc, Infar}, IFIH1 (interferon induced with helicase C domain 1) [NCBI Gene 64135] {aka AGS7, Hlcd, IDDM19, IMD95, MDA-5, MDA5}, RIGI (RNA sensor RIG-I) [NCBI Gene 23586] {aka DDX58, RIG-I, RIG1, RLR-1, SGMRT2}, ATF2 (activating transcription factor 2) [NCBI Gene 1386] {aka CRE-BP1, CREB-2, CREB2, HB16, TREB7}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, Atp6ap2 (ATPase, H+ transporting, lysosomal accessory protein 2) [NCBI Gene 70495] {aka (P)RR, 5730403E06Rik, APT6M8-9, ATP6M8-9, Atp6ip2, M8-9}, Tst (thiosulfate sulfurtransferase, mitochondrial) [NCBI Gene 22117] {aka rhodanese}, JUN (Jun proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 3725] {aka AP-1, AP1, c-Jun, cJUN, p39}, Zbtb16 (zinc finger and BTB domain containing 16) [NCBI Gene 235320] {aka PLZF, Zfp145, lu}, Ifnl3 (interferon lambda 3) [NCBI Gene 338374] {aka IFL-1, IL-28B, INF-alpha, INF-lambda, If1ia2, Il28}, HNRNPL (heterogeneous nuclear ribonucleoprotein L) [NCBI Gene 3191] {aka HNRPL, P/OKcl.14, hnRNP-L}, IFNL2 (interferon lambda 2) [NCBI Gene 282616] {aka IFNL2a, IFNL3a, IL-28A, IL28A}, PTPN1 (protein tyrosine phosphatase non-receptor type 1) [NCBI Gene 5770] {aka PTP1B}, BRD4 (bromodomain containing 4) [NCBI Gene 23476] {aka CAP, CDLS6, FSHRG4, HUNK1, HUNKI, MCAP}, TRIM25 (tripartite motif containing 25) [NCBI Gene 7706] {aka EFP, RNF147, Z147, ZNF147}, OAS2 (2'-5'-oligoadenylate synthetase 2) [NCBI Gene 4939] {aka AIAISD2}, Cxcl10 (C-X-C motif chemokine ligand 10) [NCBI Gene 15945] {aka C7, CRG-2, INP10, IP-10, IP10, Ifi10}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, Cuedc2 (CUE domain containing 2) [NCBI Gene 67116] {aka 3010002G01Rik}, Atg7 (autophagy related 7) [NCBI Gene 74244] {aka 1810013K23Rik, Agp7, Apg7l, Atg7l, Gm21553}, Oas1b (2'-5' oligoadenylate synthetase 1B) [NCBI Gene 23961] {aka Flv, L1, Mmu-L1, Oas1, Oias-2, Oias2}, TBK1 (TANK binding kinase 1) [NCBI Gene 29110] {aka AIARV, FTDALS4, IIAE8, NAK, T2K}
- **Diseases:** lung inflammation (MESH:D011014), PTP1B deficiency (MESH:C562645), IAV infection (MESH:D007251), inflammatory (MESH:D007249), injury to (MESH:D014947), Epstein-Barr virus (MESH:D020031), acute lung injury (MESH:D055371), emphysema (MESH:D004646), interstitial pneumonia (MESH:D017563), hypersensitivity (MESH:D004342), pulmonary fibrosis (MESH:D011658), pulmonary bacterial infection (MESH:D001424), viral infection (MESH:D014777), weight loss (MESH:D015431), infection (MESH:D007239), COVID-19 (MESH:D000086382)
- **Chemicals:** Poly (I:C) (MESH:D011070), LPS (MESH:D008070), CHROMR (-)
- **Species:** Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], H9N2 subtype (serotype) [taxon 102796], H1N1 subtype (serotype) [taxon 114727], human metapneumovirus (no rank) [taxon 162145], Sus scrofa (pig, species) [taxon 9823], Human alphaherpesvirus 1 (Herpes simplex virus type 1, no rank) [taxon 10298], Mus musculus (house mouse, species) [taxon 10090], Sendai virus [taxon 11191], Influenza A virus (no rank) [taxon 11320], Vesicular stomatitis virus (species) [taxon 11276], Respiratory syncytial virus (no rank) [taxon 12814], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** A549 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_0023), 293T — Homo sapiens (Human), Transformed cell line (CVCL_0063), THP-1 — Homo sapiens (Human), Childhood acute monocytic leukemia, Cancer cell line (CVCL_0006), C57BL/6 — Mus musculus (Mouse), Transformed cell line (CVCL_C0MU)

## Full text

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## Figures

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## References

85 references — full list in the complete paper: https://tomesphere.com/paper/PMC12944882/full.md

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Source: https://tomesphere.com/paper/PMC12944882