期刊
CELL HOST & MICROBE
卷 24, 期 2, 页码 234-+出版社
CELL PRESS
DOI: 10.1016/j.chom.2018.07.004
关键词
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资金
- USC Office of Research
- Norris Medical Library
- NIH [R35DE027556, R01DE026003, R01CA221521, R21AI134105, P01CA180779, R01GM093086, F30AI112277]
- Joint Research Fund for Oversea Chinese, Hong Kong and Macao Scholars [81528011]
- National Key Research and Development Program of China [2016YFD0500300, 2016YFC1200200]
- Norris Cancer Center [P30CA014089-34]
Herpes simplex virus 1 (HSV-1) establishes infections in humans and mice, but some non-human primates exhibit resistance via unknown mechanisms. Innate immune recognition pathways are highly conserved but are pivotal in determining susceptibility to DNA virus infections. We report that variation of a single amino acid residue in the innate immune sensor cGAS determines species-specific inactivation by HSV-1. The HSV-1 UL37 tegument protein deamidates human and mouse cGAS. Deamidation impairs the ability of cGAS to catalyze cGAMP synthesis, which activates innate immunity. HSV-1 with deamidase-deficient UL37 promotes robust antiviral responses and is attenuated in mice in a cGAS-and STING-dependent manner. Mutational analyses identified a single asparagine in human and mouse cGAS that is not conserved in many non-human primates. This residue underpins UL37-mediated cGAS deamidation and species permissiveness of HSV-1. Thus, HSV-1 mediates cGAS deamidation for immune evasion and exploits species sequence variation to disarm host defenses.
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