Functional Properties of Virus-Encoded and Virus-Regulated G Protein-Coupled Receptors

During coevolution with their hosts, viruses have developed several survival strategies that involve exploitation of 7 transmembrane spanning (7TM) G protein-coupled receptors (GPCRs). These include virus-encoded GPCRs and ligands and viral regulation of endogenous GPCRs. Many functional properties have been ascribed to virus-exploited GPCRs, and although the list of putative functions is steadily growing, the presence and/or function of virus-associated GPCRs is still poorly understood. This review focuses on three well-described functional properties of virus-associated GPCRs: (1) the immune evasion strategies, exemplified by γ1-herpesvirus-encoded BILF1 receptors, the human cytomegalovirus (HCMV)-encoded US28 receptor, and the Epstein-Barr virus (EBV)-regulated EBI2 (or GPR183); (2) the tissue tropism and virus-dissemination properties, exemplified by the murine CMV-encoded M33; and (3) the tumorigenic properties, exemplified by the human herpesvirus 8 (HHV8)-encoded ORF74, HCMV-US28, and EBV-BILF1. Given the general high “druggability” of GPCRs and the recent progress in understanding the immune evasive functions of the virus-exploited GPCRs in particular, we put special emphasis on the progress of novel antiviral therapeutic tools targeting these virus-associated GPCRs.