IFITM3 inhibits virus-triggered induction of type I interferon by mediating autophagosome-dependent degradation of IRF3

Interferon-induced transmembrane protein 3 (IFITM3) is a restriction factor that can be induced by viral infection and interferons (IFNs). It inhibits the entry and replication of many viruses, which are independent of receptor usage but dependent on processes that occur in endosomes. In this study,...

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Bibliographic Details
Published in:Cellular & molecular immunology 2018-09, Vol.15 (9), p.858-867
Main Authors: Jiang, Li-Qun, Xia, Tian, Hu, Yun-Hong, Sun, Ming-Shun, Yan, Shuang, Lei, Cao-Qi, Shu, Hong-Bing, Guo, Ji-Hua, Liu, Yu
Format: Article
Language:English
Subjects:
Antibodies
Autophagosomes - metabolism
Biomedical and Life Sciences
Biomedicine
Endosomes
HEK293 Cells
HeLa Cells
Homeostasis
Humans
Immunology
Interferon
Interferon regulatory factor 3
Interferon Regulatory Factor-3 - genetics
Interferon Regulatory Factor-3 - immunology
Interferon Type I - genetics
Interferon Type I - immunology
Medical Microbiology
Membrane Proteins - genetics
Membrane Proteins - immunology
Microbiology
Proteolysis
Ribonucleic acid
RNA
RNA Virus Infections - genetics
RNA Virus Infections - immunology
RNA Virus Infections - pathology
RNA viruses
RNA Viruses - genetics
RNA Viruses - immunology
RNA-Binding Proteins - genetics
RNA-Binding Proteins - immunology
Vaccine
Viruses
β-Interferon
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Summary:Interferon-induced transmembrane protein 3 (IFITM3) is a restriction factor that can be induced by viral infection and interferons (IFNs). It inhibits the entry and replication of many viruses, which are independent of receptor usage but dependent on processes that occur in endosomes. In this study, we demonstrate that IFITM3 plays important roles in regulating the RNA-virus-triggered production of IFN-β in a negative-feedback manner. Overexpression of IFITM3 inhibited Sendai virus-triggered induction of IFN-β, whereas knockdown of IFITM3 had the opposite effect. We also showed that IFITM3 was constitutively associated with IRF3 and regulated the homeostasis of IRF3 by mediating the autophagic degradation of IRF3. These findings suggest a novel inhibitory function of IFITM3 on the RNA-virus-triggered production of type I IFNs and cellular antiviral responses.
ISSN:1672-7681
2042-0226
2042-0226
DOI:10.1038/cmi.2017.15