Inhibition of IFN-gamma signalling by vaccinia virus protein C6: a multi-functional interferon antagonist

Vaccinia virus (VACV) encodes multiple proteins that function to inhibit both the production and downstream effects of interferons, which are critical modulators of the antiviral response. One such protein, VACV C6, inhibits both the production of type I IFN (by blocking IRF3 signalling) and the downstream effects of type I IFN (by blocking JAK-STAT signalling). Further to this, our findings suggest C6 can also inhibit the downstream effects of type II IFN of which IFN-gamma is the sole member. The observation that C6 co-immunoprecipitates with STAT1, a protein crucial in activating the downstream functions of IFN-gamma, might explain its inhibitory activity.