Equine herpesvirus-2 E10 gene product, but not its cellular homologue, activates NF-kappa B transcription factor and c-Jun N-terminal kinase

We have previously reported on the death effector domain containing E8 gene product from equine herpesvirus-a, designated FLICE inhibitory protein (v- FLIP), and on its cellular homologue, c-FLIP, which inhibit the activation of caspase-8 by death receptors, Here we report on the structure and functi on of the E10 gene product of equine herpesvirus-a, designated v-CARMEN, an d on its cellular homologue, c-CARMEN, which contain a caspase-recruiting d omain (CARD) motif, c-CARMEN is highly homologous to the viral protein in i ts N-terminal CARD motif but differs in its C-terminal extension. v-CARMEN and c-CARMEN interact directly in a CARD-dependent manner yet reveal differ ent binding specificities toward members of the tumor necrosis factor recep tor-associated factor (TRAF) family. v-CARMEN binds to TRAF6 and weakly to TRAF3 and, upon overexpression, potently induces the c-Jun N-terminal kinas e (JNK), p38, and nuclear factor (NF)-kappa B transcriptional pathways. c-C ARMEN or truncated versions thereof do not appear to induce JNK and NF-kapp a B activation by themselves, nor do they affect the JNK and NF-kappa B act ivating potential of v-CARMEN, Thus, in contrast to the cellular homologue, v-CARMEN may have additional properties in its unique C terminus that allo w for an autonomous activator effect on NF-B kappa and JNK, Through activat ion of NF-kappa B, V-CARMEN may regulate the expression of the cellular and viral genes important for viral replication.