Human Cytomegalovirus US28: a functionally selective chemokine binding receptor
Jennifer Vomaske1, J A Nelson, Daniel N Streblow
1Department of Molecular Microbiology and Immunology and The Vaccine and Gene Therapy Institute, Oregon Health and Sciences University, Portland, OR 97201, USA.
Infectious Disorders Drug Targets
|July 15, 2009
Summary
Human cytomegalovirus (HCMV) uses the US28 chemokine receptor to manipulate immune responses and promote disease. Understanding US28
Area of Science:
- Virology and Immunology
- Molecular and Cellular Biology
- Pharmacology
Background:
- Chemokines are crucial for immune cell recruitment during viral infections.
- Viruses like human cytomegalovirus (HCMV) can interfere with or exploit chemokine pathways.
- HCMV encodes unique chemokine receptor-like molecules, including the well-studied US28.
Purpose of the Study:
- To investigate the role of the HCMV-encoded US28 chemokine receptor.
- To understand US28's function as a virulence factor in HCMV-associated diseases.
- To explore the structure-function relationships of US28 for potential therapeutic targeting.
Main Methods:
- Characterization of US28 as a multi-chemokine binding receptor.
- Analysis of ligand binding and subsequent cellular signaling pathways.
- Investigation of constitutive activation of phospholipase C (PLC) and NF-kB.
Main Results:
- US28 binds ligands from two distinct chemokine classes, demonstrating functional selectivity.
- Ligand binding to US28 triggers cell migration via specific signaling pathways.
- US28 constitutively activates PLC and NF-kB signaling pathways.
Conclusions:
- HCMV US28 is a multifunctional chemokine receptor involved in viral pathogenesis.
- US28's ability to bind multiple chemokines and activate signaling pathways highlights its importance.
- Elucidating US28's structure-function relationships is key for developing targeted therapies.
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