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cGAS Is a Negative Regulator of RIG-I-Mediated IFN Response in Cyprinid Fish.

Abstract
In mammals, cyclic GMP-AMP synthase (cGAS) recognizes cytosolic dsDNA to induce the type I IFN response. However, the functional role of cGAS in the IFN response of fish remains unclear or controversial. In this study, we report that cGAS orthologs from crucian carp Carassius auratus (CacGAS) and grass carp Ctenopharyngodon idellus (CicGAS) target the dsRNA sensor retinoic acid-inducible gene I (RIG-I) for negative regulation of the IFN response. First, poly(deoxyadenylic-deoxythymidylic) acid-, polyinosinic-polycytidylic acid-, and spring viremia of carp virus-induced IFN responses were impaired by overexpression of CacGAS and CicGAS. Then, CacGAS and CicGAS interacted with CiRIG-I and CiMAVS and inhibited CiRIG-I- and CiMAVS-mediated IFN induction. Moreover, the K63-linked ubiquitination of CiRIG-I and the interaction between CiRIG-I and CiMAVS were attenuated by CacGAS and CicGAS. Finally, CacGAS and CicGAS decreased CiRIG-I-mediated the cellular antiviral response and facilitated viral replication. Taken together, data in this study identify CacGAS and CicGAS as negative regulators in RIG-I-like receptor signaling, which extends the current knowledge regarding the role of fish cGAS in the innate antiviral response.
AuthorsYu Zhou, Yi Lei, Long-Feng Lu, Dan-Dan Chen, Can Zhang, Zhuo-Cong Li, Xiao-Yu Zhou, Shun Li, Yong-An Zhang
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 207 Issue 3 Pg. 784-798 (08 01 2021) ISSN: 1550-6606 [Electronic] United States
PMID34290106 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2021 by The American Association of Immunologists, Inc.
Chemical References
  • Fish Proteins
  • Interferon Type I
  • Zebrafish Proteins
  • ddx58 protein, zebrafish
  • Nucleotidyltransferases
  • cGAS protein, human
Topics
  • Animals
  • Carps
  • Cyprinidae
  • Fish Proteins (genetics, immunology, metabolism)
  • Gene Expression Regulation
  • Goldfish
  • HEK293 Cells
  • Humans
  • Immunity, Innate (genetics)
  • Interferon Type I (metabolism)
  • Nucleotidyltransferases (genetics, immunology, metabolism)
  • Rhabdoviridae (physiology)
  • Rhabdoviridae Infections (immunology)
  • Signal Transduction
  • Ubiquitination
  • Zebrafish Proteins (genetics)

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