Overlapping Patterns of Rapid Evolution in the Nucleic Acid Sensors cGAS and OAS1 Suggest a Common Mechanism of Pathogen Antagonism and Escape

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A pathogen’s ability to infect new individuals within and across species is largely driven by its capacity to hijack cellular machinery and overcome the immune system. Pathogens have evolved multiple means to evade and shut down host immunity. Typically, mechanisms of inactivation involve direct interactions between host and pathogen factors. To escape inhibition over the course of generations, host factors frequently evolve in a manner that disrupts interactions at specific interfaces with pathogen factors. Likewise, pathogens adapt to restore such interactions, and these genetic tug-of-wars have been described as “molecular-arms races.” Here we focus on the adaptation of two critical host immune factors, cGAS and OAS that share identity in protein structures despite very limited genetic similarity. Our analysis identifies a variety of ways, including amino acid changes on protein surfaces, by which these host factors appear to escape pathogen-mediated inhibition. Surprisingly, some amino acid substitutions are located at equivalent sites suggesting that cGAS and OAS may have adapted to evade common pathogen encoded inhibitors. These data also identify protein surfaces that are targeted by viruses to inhibit host immunity. Taken together our results indicate the existence of critical, yet-to-be identified viral antagonists of cGAS and OAS.

Vyšlo v časopise: Overlapping Patterns of Rapid Evolution in the Nucleic Acid Sensors cGAS and OAS1 Suggest a Common Mechanism of Pathogen Antagonism and Escape. PLoS Genet 11(5): e32767. doi:10.1371/journal.pgen.1005203
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005203

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