First Author | Lian H | Year | 2018 |
Journal | Nat Commun | Volume | 9 |
Issue | 1 | Pages | 3349 |
PubMed ID | 30135424 | Mgi Jnum | J:271802 |
Mgi Id | MGI:6209107 | Doi | 10.1038/s41467-018-05559-w |
Citation | Lian H, et al. (2018) ZCCHC3 is a co-sensor of cGAS for dsDNA recognition in innate immune response. Nat Commun 9(1):3349 |
abstractText | Cyclic GMP-AMP synthase (cGAS) senses double-strand (ds) DNA in the cytosol and then catalyzes synthesis of the second messenger cGAMP, which activates the adaptor MITA/STING to initiate innate antiviral response. How cGAS activity is regulated remains enigmatic. Here, we identify ZCCHC3, a CCHC-type zinc-finger protein, as a positive regulator of cytosolic dsDNA- and DNA virus-triggered signaling. We show that ZCCHC3-deficiency inhibits dsDNA- and DNA virus-triggered induction of downstream effector genes, and that ZCCHC3-deficient mice are more susceptible to lethal herpes simplex virus type 1 or vaccinia virus infection. ZCCHC3 directly binds to dsDNA, enhances the binding of cGAS to dsDNA, and is important for cGAS activation following viral infection. Our results suggest that ZCCHC3 is a co-sensor for recognition of dsDNA by cGAS, which is important for efficient innate immune response to cytosolic dsDNA and DNA virus. |