Abstract
Chemokines are small cytokines that are part of a large family of molecules that bind to G-protein coupled receptors, which, as a family, are the most widely targeted group of molecules in the treatment of disease. Chemokines are critical for recruiting and activating the cells of the immune system during inflammation especially during viral infections. However, a number of viruses including the large herpes virus human cytomegalovirus (HCMV) encode mechanisms to impede the effects of chemokines or has gained the ability to use these molecules to its own advantage. The Human Cytomegalovirus (HCMV)-encoded chemokine receptor US28 is the best characterized of the four unique chemokine receptor-like molecules found in the HCMV genome. US28 has been studied as an important virulence factor for HCMVmediated vascular disease and, more recently, in models of HCMV-associated malignancy. US28 is a rare multichemokine family binding receptor with the ability to bind ligands from two distinct chemokine classes. Ligand binding to US28 activates cell-type and ligand-specific signaling pathways leading to cellular migration, which is an important example of receptor functional selectivity. Additionally, US28 has been demonstrated to constitutively activate phospholipase C (PLC) and NF-κB signaling pathways. Understanding the structure/function relationships between US28, its ligands and intracellular signaling molecules will provide essential clues for effective pharmacological targeting of this multifunctional chemokine receptor.
Infectious Disorders - Drug Targets
Title: Human Cytomegalovirus US28: A Functionally Selective Chemokine Binding Receptor
Volume: 9 Issue: 5
Author(s): Jennifer Vomaske, Jay A. Nelson and Daniel N. Streblow
Affiliation:
Abstract: Chemokines are small cytokines that are part of a large family of molecules that bind to G-protein coupled receptors, which, as a family, are the most widely targeted group of molecules in the treatment of disease. Chemokines are critical for recruiting and activating the cells of the immune system during inflammation especially during viral infections. However, a number of viruses including the large herpes virus human cytomegalovirus (HCMV) encode mechanisms to impede the effects of chemokines or has gained the ability to use these molecules to its own advantage. The Human Cytomegalovirus (HCMV)-encoded chemokine receptor US28 is the best characterized of the four unique chemokine receptor-like molecules found in the HCMV genome. US28 has been studied as an important virulence factor for HCMVmediated vascular disease and, more recently, in models of HCMV-associated malignancy. US28 is a rare multichemokine family binding receptor with the ability to bind ligands from two distinct chemokine classes. Ligand binding to US28 activates cell-type and ligand-specific signaling pathways leading to cellular migration, which is an important example of receptor functional selectivity. Additionally, US28 has been demonstrated to constitutively activate phospholipase C (PLC) and NF-κB signaling pathways. Understanding the structure/function relationships between US28, its ligands and intracellular signaling molecules will provide essential clues for effective pharmacological targeting of this multifunctional chemokine receptor.
Export Options
About this article
Cite this article as:
Vomaske Jennifer, Nelson A. Jay and Streblow N. Daniel, Human Cytomegalovirus US28: A Functionally Selective Chemokine Binding Receptor, Infectious Disorders - Drug Targets 2009; 9 (5) . https://dx.doi.org/10.2174/187152609789105696
DOI https://dx.doi.org/10.2174/187152609789105696 |
Print ISSN 1871-5265 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-3989 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
The Development of Targeted Therapies for Hepatocellular Cancer
Current Pharmaceutical Design Potential Role of Polyphenols in the Prevention of Cardiovascular Diseases: Molecular Bases
Current Medicinal Chemistry Advances in Antithrombotic Agents
Cardiovascular & Hematological Agents in Medicinal Chemistry Current Status of Renal Arterial Endovascular Interventions
Current Hypertension Reviews Recent Patents on Hypocholesterolemic Therapeutic Strategies: An Update
Recent Advances in DNA & Gene Sequences (Discontinued) A Glance Over the Cannabinoid Machinery to Design New Anti- Angiogenic Compounds
Mini-Reviews in Medicinal Chemistry Critical Congenital Heart Disease in Neonates: A Review Article
Current Pediatric Reviews Nutrition, Brain Aging, and Alzheimers Disease
Current Nutrition & Food Science Recent Development of Multifunctional Agents as Potential Drug Candidates for the Treatment of Alzheimer’s Disease
Current Medicinal Chemistry Imaging Reporters and Multimodal Molecular Bio-Imaging: A Database of Available Probes for Multi-Modality Bio-Imaging of Reporter Gene Expression
Recent Patents on Medical Imaging Subject Index to Volume 9
Current Pharmaceutical Design Incretins and Preservation of Endothelial Function
Cardiovascular & Hematological Agents in Medicinal Chemistry The Pathogenic Subpopulation of Th17 Cells in Obesity
Current Pharmaceutical Design Post-Translational Protein Modifications of Rare and Unconventional Types: Implications in Functions and Diseases
Current Medicinal Chemistry Protein Kinase C – Possible Therapeutic Target to Treat Cardiovascular Diseases
Cardiovascular & Hematological Disorders-Drug Targets Enhancing Cardiovascular Dynamics by Inhibition of Thrombospondin- 1/CD47 Signaling
Current Drug Targets Regeneration of Pancreatic β-Cells in vivo as a Potential Therapeutic Approach for Diabetes Mellitus
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Nitric Oxide Signaling and the Cross Talk with Prostanoids Pathways in Vascular System
Medicinal Chemistry Pharmacological Treatment of Attention Deficit Hyperactivity Disorder (ADHD): A Systematic Review of Recent Data
Current Psychopharmacology The Intermediate-Conductance Ca2+-Activated K+ Channel (KCa3.1) in Vascular Disease
Cardiovascular & Hematological Agents in Medicinal Chemistry