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.
© 2019 John Wiley & Sons Ltd.
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