A Novel Family of Viral Death Effector Domain-containing Molecules That Inhibit Both CD-95- and Tumor Necrosis Factor Receptor-1-induced Apoptosis

• DOI: 10.1074/jbc.272.15.9621
• Publication Date: 2002-07-26T15:07:12Z
• Authors: Shimin Hu; Claudius Vincenz; Mark Buller; Vishva M. Dixit
• Keywords: FADD; TRADD; Caspase 8; Inhibitor of apoptosis

Molluscum contagiosum virus proteins MC159 and MC160 the equine herpesvirus 2 protein E8 share substantial homology to death effector domain present in adaptor molecule Fas-associated (FADD) initiating protease FADD-like interleukin-1β-converting enzyme (FLICE) (caspase-8). FADD FLICE participate generating signal from both tumor necrosis factor receptor-1 (TNFR-1) CD-95 receptor. The flow of signals TNFR-1 occurs through receptor-associated (TRADD) FLICE, whereas for receptor directly communicates with then FLICE. inhibited TNFR-1- CD-95-induced apoptosis as well killing mediated by overexpression downstream adaptors TRADD FADD. Neither viral molecule, however, FLICE-induced killing, consistent an inhibitory action upstream active protease. These data suggest existence a novel strategy employed viruses attenuate host immune mechanisms. Given that bovine 4 E1.1 Kaposi's sarcoma associated-herpesvirus K13 also possess significant molecules MC159, MC160, E8, it may be this class is used ubiquitously evade defense.