Species-Specific Deamidation of cGAS by Herpes Simplex Virus UL37 Protein Facilitates Viral Replication.
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.
PMID: 30092200 [PubMed - in process]
Source: Cell Host and Microbe - Category: Microbiology Authors: Zhang J, Zhao J, Xu S, Li J, He S, Zeng Y, Xie L, Xie N, Liu T, Lee K, Seo GJ, Chen L, Stabell AC, Xia Z, Sawyer SL, Jung J, Huang C, Feng P Tags: Cell Host Microbe Source Type: research