Abstract
In the past two decades, emerging studies have suggested that DExD/H box helicases belonging to helicase superfamily 2 (SF2) play essential roles in antiviral innate immunity. However, the antiviral functions of helicase SF1, which shares a conserved helicase core with SF2, are little understood. Here we demonstrate that zinc finger NFX1-type containing 1 (ZNFX1), a helicase SF1, is an interferon (IFN)-stimulated, mitochondrial-localised dsRNA sensor that specifically restricts the replication of RNA viruses. Upon virus infection, ZNFX1 immediately recognizes viral RNA through its Armadillo-type fold and P-loop domain and then interacts with mitochondrial antiviral signalling protein to initiate the type I IFN response without depending on retinoic acid-inducible gene I-like receptors (RLRs). In short, as is the case with interferon-stimulated genes (ISGs) alone, ZNFX1 can induce IFN and ISG expression at an early stage of RNA virus infection to form a positively regulated loop of the well-known RLR signalling. This provides another layer of understanding of the complexity of antiviral immunity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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A549 Cells
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Adaptor Proteins, Signal Transducing / genetics*
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Adaptor Proteins, Signal Transducing / immunology
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Amino Acid Sequence
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Animals
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Antigens, Neoplasm / genetics*
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Antigens, Neoplasm / immunology
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DEAD Box Protein 58 / genetics
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DEAD Box Protein 58 / immunology
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Gene Expression Regulation
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HEK293 Cells
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Host-Pathogen Interactions
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Humans
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Immunity, Innate
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Interferon Type I / genetics
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Interferon Type I / immunology
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Macrophages, Peritoneal / drug effects
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Macrophages, Peritoneal / immunology
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Macrophages, Peritoneal / virology
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Mice
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Mice, Knockout
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Mitochondria / drug effects
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Mitochondria / immunology*
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Mitochondria / virology
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Nucleic Acid Conformation
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Poly I-C / pharmacology
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Primary Cell Culture
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Protein Binding
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RNA Splicing Factors / genetics*
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RNA Splicing Factors / immunology
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RNA, Double-Stranded / chemistry
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RNA, Double-Stranded / genetics*
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RNA, Double-Stranded / immunology
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RNA, Viral / chemistry
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RNA, Viral / genetics*
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RNA, Viral / immunology
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RNA-Binding Proteins / genetics
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RNA-Binding Proteins / metabolism*
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Sequence Alignment
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Sequence Homology, Amino Acid
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Signal Transduction
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Transcription Factors, General / genetics
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Transcription Factors, General / metabolism*
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Vesiculovirus / genetics*
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Vesiculovirus / growth & development
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Vesiculovirus / immunology
Substances
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Adaptor Proteins, Signal Transducing
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Antigens, Neoplasm
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IPS-1 protein, mouse
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Interferon Type I
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RNA Splicing Factors
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RNA, Double-Stranded
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RNA, Viral
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RNA-Binding Proteins
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Sf1 protein, mouse
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Transcription Factors, General
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ZNFX1 protein, human
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Znfx1 protein, mouse
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Ddx58 protein, mouse
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DEAD Box Protein 58
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Poly I-C