1. Cyclic GMP-AMP synthase is essential for cytosolic double-stranded DNA and fowl adenovirus serotype 4 triggered innate immune responses in chickens.
- Author
-
Wang J, Ba G, Han YQ, Ming SL, Wang MD, Fu PF, Zhao QQ, Zhang S, Wu YN, Yang GY, and Chu BB
- Subjects
- Amino Acid Sequence, Animals, Cell Line, DNA Damage, Etoposide pharmacology, Gene Expression Profiling, Interferon Regulatory Factor-7 metabolism, Interferon-beta metabolism, Interleukin-1beta metabolism, Nucleotides, Cyclic chemistry, Phylogeny, Protein Structure, Secondary, Protein Structure, Tertiary, Signal Transduction drug effects, Subcellular Fractions metabolism, Adenoviridae immunology, Chickens immunology, Chickens virology, Cytosol metabolism, DNA metabolism, Immunity, Innate, Nucleotides, Cyclic metabolism, Serogroup
- Abstract
Cyclic GMP-AMP (cGAMP) synthase (cGAS) is a predominant DNA sensor inducing the activation of the innate immune responses that produce proinflammatory cytokines and type I interferons, which has been well-investigated in mammals. However, chicken cGAS (chcGAS), which participates in avian innate immunity, has not been well-investigated. Here, we cloned the complete open reading frame sequence of chcGAS. Multiple sequence alignment and phylogenetic analysis revealed that chcGAS was homologous to mammalian cGAS. The chcGAS mRNA was highly expressed in the bone marrow and ileum. The subcellular localization of chcGAS was mainly in the cytoplasm, and partial co-localization was observed in the endoplasmic reticulum. Through overexpression and RNA interference, we demonstrated that chcGAS responded to exogenous dsDNA, HS-DNA, and poly(dA:dT), and to self dsDNA from the DNA damage response, thereby triggering the activation of STING/TBK1/IRF7-mediated innate immunity in both chicken embryonic fibroblasts and chicken liver cancer cells. Furthermore, downregulation of chcGAS enhanced the infection of fowl adenovirus serotype 4 in LMH cells. Our results demonstrated that chcGAS was an important cytosolic DNA sensor activating innate immune responses and may shed light on a strategy for preventing infectious diseases in the poultry industry., (Copyright © 2020. Published by Elsevier B.V.)
- Published
- 2020
- Full Text
- View/download PDF