Journal Article

Mitochondria-localised ZNFX1 functions as a dsRNA sensor to initiate antiviral responses through MAVS

Wang, Yao, Jia, Xin, Ling, Tao, Lan, Xihong, Xu, Anlong, Yuan, Shaochun, Nie, Meng, Ge, Yong, Chen, Shangwu

2019

Overview

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. Wang et al. identify ZNFX1 as a mitochondria-localised sensor that recognizes viral dsRNA and induces a type I interferon response, thereby restricting virus infection.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 38/89 / 38/91 / 45/77 / 631/250 / 631/250/262 / 631/250/516 / 631/80/642/333 / 64/60 / 96/1 / 96/109 / 96/21 / 96/31 / 96/44 / 96/63 / A549 Cells / Adaptor Proteins, Signal Transducing - genetics / Adaptor Proteins, Signal Transducing - immunology / Amino Acid Sequence / Animals / Antigens, Neoplasm - genetics / Antigens, Neoplasm - immunology / Antiviral drugs / Biological response modifiers / Biomedical and Life Sciences / Cancer Research / Cell Biology / DEAD Box Protein 58 - genetics / DEAD Box Protein 58 - immunology / Developmental Biology / DNA binding proteins / DNA helicase / Double-stranded RNA / Gene expression / Gene Expression Regulation / Genes / Health aspects / HEK293 Cells / Host-Pathogen Interactions / Humans / Immunity / Immunity, Innate / Infection / Innate immunity / Interferon / Interferon Type I - genetics / Interferon Type I - immunology / Life Sciences / Macrophages, Peritoneal - drug effects / Macrophages, Peritoneal - immunology / Macrophages, Peritoneal - virology / Mice / Mice, Knockout / Mitochondria / Mitochondria - drug effects / Mitochondria - immunology / Mitochondria - virology / Nucleic Acid Conformation / Poly I-C - pharmacology / Primary Cell Culture / Protein Binding / Protein folding / Receptors / Retinoic acid / Ribonucleic acid / RNA / RNA Splicing Factors - genetics / RNA Splicing Factors - immunology / RNA viruses / RNA, Double-Stranded - chemistry / RNA, Double-Stranded - genetics / RNA, Double-Stranded - immunology / RNA, Viral - chemistry / RNA, Viral - genetics / RNA, Viral - immunology / RNA-Binding Proteins - genetics / RNA-Binding Proteins - metabolism / Sequence Alignment / Sequence Homology, Amino Acid / Signal Transduction / Signaling / Stem Cells / Transcription Factors, General - genetics / Transcription Factors, General - metabolism / Vesiculovirus - genetics / Vesiculovirus - growth & development / Vesiculovirus - immunology / Virus diseases / Viruses / Zinc finger proteins