Why Are Cytomegalovirus-Encoded G-Protein-Coupled Receptors Essential for Infection but Only Variably Conserved?

Abstract

Cytomegaloviruses (CMVs) encode viral G-protein-coupled receptors (vGPCRs) that have diverged from their cellular homologues to perform new functions. Human cytomegalovirus (HCMV) encodes four vGPCRs: UL33, UL78, US27, and US28, which contribute to viral pathogenesis, cellular signalling, and latency. While the role of US28 in chemokine signalling and viral latency is well characterised, the functions of other vGPCRs remain incompletely understood. Rodent cytomegaloviruses only have homologues to UL33 and UL78, while primates have two to five additional GPCRs which are homologues of US27 and US28. Different CMVs appear to have evolved vGPCRs with functions specific to infection of their respective host. As non-human CMVs are used as model organisms to understand clinical cytomegalovirus disease and develop vaccines and antivirals, understanding the differences between these vGPCRs helps researchers understand critical differences between their models. This review aims to address the differences between CMV vGPCRs, and how these differences may affect models of CMV disease to facilitate future research.