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

Abstract

We have previously reported on the death effector domain containing E8 gene product from equine herpesvirus-2, 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-2, 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 vital 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)-κB transcriptional pathways, c-CARMEN or truncated versions thereof do not appear to induce JNK and NF-κB activation by themselves, nor do they affect the JNK and NF-κB 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-κB and JNK. Through activation of NF-κB, v-CARMEN may regulate the expression of the cellular and viral genes important for viral replication.