Figure 8.

Synergistic activation of viperin, IRAK1, and TRAF6 couples the production of antiviral ribonucleotides with innate immune signaling. Clockwise from the top: binding of SAM and CTP to the viperin-IRAK1-TRAF6 complex activates the complex toward poly-ubiquitination of IRAK1. Activated viperin catalyzes the reaction of SAM with CTP to form 5′-dA and ddhCTP and concomitantly switches the complex from the ubiquitination-active state to ubiquitination-inactive state. Poly-ubiquitinated IRAK1 dissociates from the complex, leading to up-regulation of INF-1. For discussion see the text.