title: The HCMV US28 vGPCR induces potent Gαq/PLC-β signaling in monocytes leading to increased adhesion to endothelial cells.
abstract: US28 transcripts have been detected in primary monocytes and in THP-1 monocytes infected with HCMV but US28 protein expression has not yet been demonstrated in these cell types. Moreover, the mechanism(s) by which US28 signals and contributes to viral pathogenesis in monocytes remains unclear. Here, we show that US28 protein is robustly expressed in HCMV infected THP-1 monocytes and that US28 can trigger Gαq dependent signaling in THP-1 cells infected with HCMV and in THP-1 cells stably expressing US28. US28 signaling in these cells is dependent on G-protein coupling, but independent of chemokine binding. Importantly, we demonstrate that this US28 signaling is functionally important as it stimulates the adhesion of monocytes to an endothelial monolayer. Our studies, which demonstrate that US28-driven Gαq signaling has profound effects on monocyte biology, suggest that US28 driven phenotypic changes in HCMV infected monocytes may play important roles in HCMV dissemination and/or pathogenesis.
authors: Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267-0524, USA.
authors: Shu-En
authors: SE
authors: Wu
authors: Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267-0524, USA. Electronic address: william.miller@uc.edu.
authors: William E
authors: WE
authors: Miller
mesh_terms: D002448:Cell Adhesion; D002460:Cell Line; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000378:metabolism / Q000821:virology; D042783:Endothelial Cells / Q000378:metabolism*; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism*; D006801:Humans; D009000:Monocytes / Q000502:physiology* / Q000821:virology*; D054799:Phospholipase C beta / Q000378:metabolism*; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D019707:Receptors, Chemokine; C411191:US28 receptor, Cytomegalovirus; D014764:Viral Proteins; D054799:Phospholipase C beta; D043802:GTP-Binding Protein alpha Subunits, Gq-G11
keywords: Cytomegalovirus; Endothelial adhesion; Gαq; HCMV; Latency; Lytic replication; Macrophages; Monocytes; US28; vGPCR