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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Vydáno v:	Science (American Association for the Advancement of Science) Ročník 365; číslo 6454
Hlavní autoři:	Wang, Lei, Wen, Mingyue, Cao, Xuetao
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States 16.08.2019
Témata:	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
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1095-9203 1095-9203
DOI:	10.1126/science.aav0758