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ZCCHC3 is a co-sensor of cGAS for dsDNA recognition in innate immune response
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-typ...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6105683/ https://www.ncbi.nlm.nih.gov/pubmed/30135424 http://dx.doi.org/10.1038/s41467-018-05559-w |
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author | Lian, Huan Wei, Jin Zang, Ru Ye, Wen Yang, Qing Zhang, Xia-Nan Chen, Yun-Da Fu, Yu-Zhi Hu, Ming-Ming Lei, Cao-Qi Luo, Wei-Wei Li, Shu Shu, Hong-Bing |
author_facet | Lian, Huan Wei, Jin Zang, Ru Ye, Wen Yang, Qing Zhang, Xia-Nan Chen, Yun-Da Fu, Yu-Zhi Hu, Ming-Ming Lei, Cao-Qi Luo, Wei-Wei Li, Shu Shu, Hong-Bing |
author_sort | Lian, Huan |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6105683 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-61056832018-08-27 ZCCHC3 is a co-sensor of cGAS for dsDNA recognition in innate immune response Lian, Huan Wei, Jin Zang, Ru Ye, Wen Yang, Qing Zhang, Xia-Nan Chen, Yun-Da Fu, Yu-Zhi Hu, Ming-Ming Lei, Cao-Qi Luo, Wei-Wei Li, Shu Shu, Hong-Bing Nat Commun Article 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. Nature Publishing Group UK 2018-08-22 /pmc/articles/PMC6105683/ /pubmed/30135424 http://dx.doi.org/10.1038/s41467-018-05559-w Text en © The Author(s) 2018, corrected publication 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Lian, Huan Wei, Jin Zang, Ru Ye, Wen Yang, Qing Zhang, Xia-Nan Chen, Yun-Da Fu, Yu-Zhi Hu, Ming-Ming Lei, Cao-Qi Luo, Wei-Wei Li, Shu Shu, Hong-Bing ZCCHC3 is a co-sensor of cGAS for dsDNA recognition in innate immune response |
title | ZCCHC3 is a co-sensor of cGAS for dsDNA recognition in innate immune response |
title_full | ZCCHC3 is a co-sensor of cGAS for dsDNA recognition in innate immune response |
title_fullStr | ZCCHC3 is a co-sensor of cGAS for dsDNA recognition in innate immune response |
title_full_unstemmed | ZCCHC3 is a co-sensor of cGAS for dsDNA recognition in innate immune response |
title_short | ZCCHC3 is a co-sensor of cGAS for dsDNA recognition in innate immune response |
title_sort | zcchc3 is a co-sensor of cgas for dsdna recognition in innate immune response |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6105683/ https://www.ncbi.nlm.nih.gov/pubmed/30135424 http://dx.doi.org/10.1038/s41467-018-05559-w |
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