Equine Herpesvirus-2 E10 Gene Product, but Not Its Cellular Homologue, Activates NF-κB 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 function of the E10 gene product of equine herpesvirus-a, designated v-CARMEN, and on its cellular homologue, c-CARMEN, which contain a caspase-recruiting domain (CARD) motif, c-CARMEN is highly homologous to the viral protein in its 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 different binding specificities toward members of the tumor necrosis factor receptor-associated factor (TRAF) family. v-CARMEN binds to TRAF6 and weakly to TRAF3 and, upon overexpression, potently induces the c-Jun N-terminal kinase (JNK), p38, and nuclear factor (NF)-kappa B transcriptional pathways. c-CARMEN or truncated versions thereof do not appear to induce JNK and NF-kappa B activation by themselves, nor do they affect the JNK and NF-kappa B activating potential of v-CARMEN, Thus, in contrast to the cellular homologue, v-CARMEN may have additional properties in its unique C terminus that allow for an autonomous activator effect on NF-B kappa and JNK, Through activation of NF-kappa B, V-CARMEN may regulate the expression of the cellular and viral genes important for viral replication.