In this work, the authors used the CRISPR system to define cellular proteins essential to elicitation of the antiviral activity for alphavirus, Venezuelan Equine Encephalitis virus, and Sindbis virus. Their results allowed the identification of IRF3, the IRF3-activating adaptor molecule STING, and the IFN-associated transcription factor STAT1 as required for observed gene induction and antiviral effects. In vivo stimulation of STING-dependent activity by an unrelated small molecule in a mouse model of Chikungunya virus infection blocked viremia demonstrating that pharmacologic activation of this signaling pathway may represent a feasible strategy for combating emerging Alphaviruses.
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In this work, the authors used the CRISPR system to define cellular proteins essential to elicitation of the antiviral activity for alphavirus, Venezuelan Equine Encephalitis virus, and Sindbis virus. Their results allowed the identification of IRF3, the IRF3-activating adaptor molecule STING, and the IFN-associated transcription factor STAT1 as required for observed gene induction and antiviral effects. In vivo stimulation of STING-dependent activity by an unrelated small molecule in a mouse model of Chikungunya virus infection blocked viremia demonstrating that pharmacologic activation of this signaling pathway may represent a feasible strategy for combating emerging Alphaviruses.