Nuclear hnRNPA2B1 initiates and amplifies the innate immune response to DNA viruses

DNA viruses typically eject genomic DNA into the nuclei of host cells after entry. It is unclear, however, how nuclear pathogen-derived DNA triggers innate immune responses. We report that heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) recognizes pathogenic DNA and amplifies interferon-α/β...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) Vol. 365; no. 6454
Main Authors: Wang, Lei, Wen, Mingyue, Cao, Xuetao
Format: Journal Article
Language:English
Published: United States 16.08.2019
Subjects:
Adenosine - analogs & derivatives
Adenosine - metabolism
Animals
Cell Nucleus - immunology
Cell Nucleus - virology
Cytoplasm - metabolism
DNA Virus Infections - immunology
DNA, Viral - immunology
HEK293 Cells
Herpesvirus 1, Human - immunology
Heterogeneous-Nuclear Ribonucleoprotein Group A-B - genetics
Heterogeneous-Nuclear Ribonucleoprotein Group A-B - metabolism
Humans
Immunity, Innate
Interferon Regulatory Factor-3
Interferon-alpha - metabolism
Interferon-beta - metabolism
Jumonji Domain-Containing Histone Demethylases - metabolism
Membrane Proteins - metabolism
Mice
Mice, Knockout
Nuclear Proteins - metabolism
Nucleotidyltransferases - metabolism
Phosphoproteins - metabolism
Protein Transport
Protein-Serine-Threonine Kinases - metabolism
RAW 264.7 Cells
ISSN:1095-9203, 1095-9203
Online Access:Get more information
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Summary:DNA viruses typically eject genomic DNA into the nuclei of host cells after entry. It is unclear, however, how nuclear pathogen-derived DNA triggers innate immune responses. We report that heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) recognizes pathogenic DNA and amplifies interferon-α/β (IFN-α/β) production. Upon DNA virus infection, nuclear-localized hnRNPA2B1 senses viral DNA, homodimerizes, and is then demethylated at arginine-226 by the arginine demethylase JMJD6. This results in hnRNPA2B1 translocation to the cytoplasm where it activates the TANK-binding kinase 1-interferon regulatory factor 3 (TBK1-IRF3) pathway, leading to IFN-α/β production. Additionally, hnRNPA2B1 facilitates -methyladenosine (m A) modification and nucleocytoplasmic trafficking of , , and messenger RNAs. This, in turn, amplifies the activation of cytoplasmic TBK1-IRF3 mediated by these factors. Thus, hnRNPA2B1 plays important roles in initiating IFN-α/β production and enhancing stimulator of interferon genes (STING)-dependent cytoplasmic antiviral signaling.
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ISSN:1095-9203
1095-9203
DOI:10.1126/science.aav0758