Herpesvirus-encoded GPCRs rewire cellular signaling.

Viral G-protein-coupled receptors (vGPCRs) are chemokine receptor homologues encoded by the Herpes- and Capripoxviridae. They are thought to have been hijacked from the host genome during the course of evolution. These vGPCRs play different roles in the viral lifecycle and associated pathologies. Three members of the Herpesviridae, Kaposi sarcoma-associated herpesvirus (KSHV), Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) are capable of setting up persistent latent infections in humans. Two of the herpesviruses, KSHV and EBV, are associated with cancer, while HCMV may have an oncomodulary effect. The vGPCRs may contribute to the escape of immune surveillance and (constitutively) activate signaling pathways linked to proliferation and inflammation. Some vGPCRs induce activation of autocrine and paracrine signaling, resulting in secretion of growth factors and/or cytokines. As a result, vGPCRs effectively rewire cellular signaling networks. Delineating the cellular signaling networks modulated by these vGPCRs will be crucial for treatment of virus-associated pathologies.