SPI-2/CrmA (cytokine response modifier A) is a poxvirus gene product with homology to members of the serpin (serine protease inhibitor) superfamily. Cowpox virus-derived and vaccinia virus-derived CrmA cDNAs transfected into cells inhibit apoptosis induced by Fas-ligation and activation of TNFR1 (Tewari M and Dixit VM 1995; Miura M et al, 1995; Kettle S et al. 1997). Cowpox virus-derived CrmA was shown to selectively inhibit caspases in Fas-mediated apoptosis, showing the highest affinity for interleukin-1 beta-converting enzyme (ICE) and a similarly high affinity for caspase-8, Ki = 0.95 nM (Zhou Q et al. 1997).