Role of ORF74-Encoded Viral G Protein-Coupled Receptor in Human Herpesvirus 8 Lytic Replication

The human herpesvirus 8 (HHV-8) viral G protein-coupled receptor (vGPCR) has been implicated in virus-associated disease pathogenesis due principally to its ability to induce the production of angiogenic cytokines involved in this process. However, the role of the vGPCR in normal virus biology is understudied and remains unknown. Here we provide evidence from vGPCR gene knockout and depletion experiments that vGPCR is a positive regulator of HHV-8 productive replication and, through experimental utilization of Gα-coupling variants of vGPCR, that signaling via Gαq activation and targeted mitogen-activated protein kinase pathways is of particular relevance to this activity.