RSAD2 and infection: 25 Finally, CIAO1 has been shown to be instrumental in the maturation of the radical S-adenosylmethionine (SAM) protein viperin, and the iron-sulfur cluster of viperin is obligatory for its antiviral activity against many different viruses.4,26 The critical function of the CIA machinery for antiviral host defense, and its loss may well explain the recurrent severe infections occurring in our CIAO1- and MMS19-deficient patients.