title: Partial functional complementation between human and mouse cytomegalovirus chemokine receptor homologues.
abstract: The human cytomegalovirus (CMV) proteins US28 and UL33 are homologous to chemokine receptors (CKRs). Knockout of the mouse CMV M33 protein (UL33 homologue) results in substantial attenuation of salivary gland infection/replication and reduced efficiency of reactivation from tissue explants. M33-mediated G protein-coupled signaling is critical for the salivary gland phenotype. In this report, we demonstrate that US28 and (to a lesser degree) UL33 restore reactivation from tissue explants and partially restore replication in salivary glands (compared to a signaling-deficient M33 mutant). These studies provide a novel small animal model for evaluation of therapies targeting the human CMV CKRs.
authors.affiliation: The University of Queensland, Clinical Medical Virology Centre, and Royal Children's Hospital, Sir Albert Sakzewski Virus Research Centre, Queensland, Australia.
authors.forename: Helen E
authors.initials: HE
authors.lastname: Farrell
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Abraham
authors.forename: Rhonda D
authors.initials: RD
authors.lastname: Cardin
authors.forename: Alexander H
authors.initials: AH
authors.lastname: Sparre-Ulrich
authors.forename: Mette M
authors.initials: MM
authors.lastname: Rosenkilde
authors.forename: Katja
authors.initials: K
authors.lastname: Spiess
authors.forename: Tine H
authors.initials: TH
authors.lastname: Jensen
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Kledal
authors.forename: Nicholas
authors.initials: N
authors.lastname: Davis-Poynter
mesh_terms: D000818:Animals; D003587:Cytomegalovirus / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000821:virology; D004195:Disease Models, Animal; D005260:Female; D006566:Herpesviridae Infections / Q000821:virology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D018146:Muromegalovirus / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009928:Organ Specificity; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D012469:Salivary Glands / Q000378:metabolism / Q000821:virology; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014775:Virus Activation; D017735:Virus Latency; D014779:Virus Replication
chemical_list: D019707:Receptors, Chemokine; C411191:US28 receptor, Cytomegalovirus; D014764:Viral Proteins