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

Abstract

A nuclear sensor of viral DNA? A signaling pathway in eukaryotes known as cGAS–STING recognizes the presence of cytosolic DNA, which alerts the immune system to viral infection or cellular damage. However, the majority of DNA viruses direct their genomic DNA into nuclei, suggesting that nuclear-specific sensing is also needed. L. Wang et al. find that during herpes simplex virus–1 infection, heterogeneous nuclear ribonucleoprotein A2B1 forms a complex with viral DNA, homodimerizes, and is demethylated. These events result in translocation of the complex to the cytosol and activation of the immune system through type I interferon signaling. Additionally, the complex promotes N 6 -methyladenosine modification and translocation of cGAS–STING–related mRNAs after DNA virus infection, further amplifying the immune response. Science , this issue p. eaav0758