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Publication : ZCCHC3 is a co-sensor of cGAS for dsDNA recognition in innate immune response.

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.
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