Deep Mutational Scanning
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Disrupting IFIT1-STAT2 viral evasion synergy yields live-attenuated flavivirus with enhanced immune priming
Diverse human viruses deploy a common immune-evasion strategy: viral 2'-O-methylation coupled with STAT2 antagonism. Yet the importance of this coupling and whether targeting the coupled functions offers benefits in vaccine development, remains unknown. Using deep mutational scanning of the dengue NS5 protein, we discovered that the two immune-evasion functions work synergistically to cripple interferon signaling.
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