Publikationsdatum:
2019
Beschreibung:
〈p〉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 IFN-α/β production. Upon DNA virus infection, nuclear-localized hnRNPA2B1 senses viral DNA, homodimerizes, and is then demethylated at Arg226 by the arginine demethylase JMJD6. This results in hnRNPA2B1 translocation to the cytoplasm where it activates the TBK1–IRF3 pathway, leading to IFN-α/β production. Additionally, hnRNPA2B1 facilitates 〈i〉N〈/i〉〈sup〉6〈/sup〉-methyladenosine (m〈sup〉6〈/sup〉A) modification and nucleocytoplasmic trafficking of 〈i〉CGAS〈/i〉, 〈i〉IFI16〈/i〉, and 〈i〉STING〈/i〉 mRNAs. This, in turn, amplifies the activation of cytoplasmic TBK1–IRF3 mediated by these factors. Thus, hnRNPA2B1 plays important roles initiating IFN-α/β production and enhancing STING-dependent cytoplasmic antiviral signaling.〈/p〉
Print ISSN:
0036-8075
Digitale ISSN:
1095-9203
Thema:
Allgemeine Naturwissenschaft
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