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

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 latenc...

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Main Authors: Suzan Fares, Benjamin A. Krishna
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Pathogens
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Online Access:https://www.mdpi.com/2076-0817/14/3/245
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author Suzan Fares
Benjamin A. Krishna
author_facet Suzan Fares
Benjamin A. Krishna
author_sort Suzan Fares
collection DOAJ
description 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.
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spelling doaj-art-87d4d59c5fea4635961f6f4ed43619732025-08-20T03:43:34ZengMDPI AGPathogens2076-08172025-03-0114324510.3390/pathogens14030245Why Are Cytomegalovirus-Encoded G-Protein-Coupled Receptors Essential for Infection but Only Variably Conserved?Suzan Fares0Benjamin A. Krishna1Occlutech Holding AG, Feldstrasse 22, 8200 Schaffhausen, SwitzerlandCambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Cambridge CB2 0AW, UKCytomegaloviruses (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.https://www.mdpi.com/2076-0817/14/3/245cytomegalovirus (CMV)G-protein coupled receptors (GPCRs)signallinganimal modelstherapeutics
spellingShingle Suzan Fares
Benjamin A. Krishna
Why Are Cytomegalovirus-Encoded G-Protein-Coupled Receptors Essential for Infection but Only Variably Conserved?
Pathogens
cytomegalovirus (CMV)
G-protein coupled receptors (GPCRs)
signalling
animal models
therapeutics
title Why Are Cytomegalovirus-Encoded G-Protein-Coupled Receptors Essential for Infection but Only Variably Conserved?
title_full Why Are Cytomegalovirus-Encoded G-Protein-Coupled Receptors Essential for Infection but Only Variably Conserved?
title_fullStr Why Are Cytomegalovirus-Encoded G-Protein-Coupled Receptors Essential for Infection but Only Variably Conserved?
title_full_unstemmed Why Are Cytomegalovirus-Encoded G-Protein-Coupled Receptors Essential for Infection but Only Variably Conserved?
title_short Why Are Cytomegalovirus-Encoded G-Protein-Coupled Receptors Essential for Infection but Only Variably Conserved?
title_sort why are cytomegalovirus encoded g protein coupled receptors essential for infection but only variably conserved
topic cytomegalovirus (CMV)
G-protein coupled receptors (GPCRs)
signalling
animal models
therapeutics
url https://www.mdpi.com/2076-0817/14/3/245
work_keys_str_mv AT suzanfares whyarecytomegalovirusencodedgproteincoupledreceptorsessentialforinfectionbutonlyvariablyconserved
AT benjaminakrishna whyarecytomegalovirusencodedgproteincoupledreceptorsessentialforinfectionbutonlyvariablyconserved