Identification of lncRNA-155 encoded by MIR155HG as a novel regulator of innate immunity against influenza A virus infection

Cell Microbiol. 2019 Aug;21(8):e13036. doi: 10.1111/cmi.13036. Epub 2019 May 29.

Abstract

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.

Keywords: MIR155HG; PTP1B; influenza A virus; innate immunity; lncRNA; miR-155.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Animals
  • Cytokines / genetics
  • Cytokines / immunology
  • Gene Expression Regulation
  • HEK293 Cells
  • Host-Pathogen Interactions / genetics
  • Host-Pathogen Interactions / immunology*
  • Humans
  • Immunity, Innate*
  • Influenza A virus / genetics
  • Influenza A virus / growth & development
  • Influenza A virus / immunology*
  • Influenza A virus / pathogenicity
  • Influenza, Human / genetics
  • Influenza, Human / immunology
  • Influenza, Human / virology
  • Interferon-Induced Helicase, IFIH1 / genetics
  • Interferon-Induced Helicase, IFIH1 / immunology
  • Interferon-beta / genetics
  • Interferon-beta / immunology
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Mice
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • MicroRNAs / immunology
  • NF-kappa B / genetics
  • NF-kappa B / immunology
  • NIH 3T3 Cells
  • Oligoribonucleotides / genetics
  • Oligoribonucleotides / metabolism
  • Orthomyxoviridae Infections / genetics*
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / mortality
  • Orthomyxoviridae Infections / virology
  • RAW 264.7 Cells
  • RNA, Long Noncoding / antagonists & inhibitors
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / immunology
  • Signal Transduction
  • Survival Analysis
  • Toll-Like Receptor 3 / genetics
  • Toll-Like Receptor 3 / immunology
  • Ubiquitins / genetics
  • Ubiquitins / immunology
  • Virus Replication / genetics
  • Virus Replication / immunology

Substances

  • Cytokines
  • MIRN155 microRNA, human
  • MicroRNAs
  • NF-kappa B
  • Oligoribonucleotides
  • RNA, Long Noncoding
  • TLR3 protein, human
  • Toll-Like Receptor 3
  • Ubiquitins
  • ISG15 protein, human
  • Interferon-beta
  • Interferon-gamma
  • IFIH1 protein, human
  • Interferon-Induced Helicase, IFIH1