DEATH EFFECTOR DOMAIN-CONTAINING HERPESVIRUS AND POXVIRUS PROTEINS INHIBIT BOTH FAS-INDUCED AND TNFR1-INDUCED APOPTOSIS

To identify novel antiapoptotic proteins encoded by DNA viruses, we se arched viral genomes for proteins that might interfere with Fas and TN FR1 apoptotic signaling pathways. We report here that equine herpesvir us type 2 E8 protein and molluscum contagiosum virus MC159 protein bot h show sequence similarity to the death effector domains (DEDs) of the Fas/TNFR1 signaling components FADD and caspase-8. Yeast two-hybrid a nalysis revealed that E8 protein interacted with the caspase-8 prodoma in whereas MC159 protein interacted with FADD, Furthermore, expression of either E8 protein or MC159 protein protected cells from Fas-and TN FR1-induced apoptosis indicating that certain herpesviruses and poxvir uses use DED-mediated interactions to interfere with apoptotic signali ng pathways, These findings identify a novel control point exploited b y viruses to regulate Fas- and TNFR1-mediated apoptosis.