Human cytomegalovirus US28 protein (US28)

Human cytomegalovirus US28 protein is a viral G protein-coupled receptor (vGPCR) encoded by the US28 gene of Human Cytomegalovirus (HCMV) (UniProt: P09704). It serves as a functional mimic of human chemokine receptors but possesses the unique ability to bind a wide array of chemokines, including both CC and CX3C classes, which it internalizes to deplete the extracellular environment (chemokine scavenging) (PMID: 25611032). A defining feature of US28 is its high level of constitutive, ligand-independent signaling, which activates multiple intracellular pathways such as PLC, PKC, and NF-kappaB to modulate the host cell environment. The protein is essential for HCMV pathogenesis, contributing to viral entry, immune evasion, and the maintenance of viral latency in myeloid progenitor cells. In clinical research, US28 has been identified as an oncomodulator, particularly in glioblastoma, where it promotes tumor progression by enhancing cell survival, migration, and angiogenesis (PMID: 30617331). Because it is expressed on the surface of infected cells and certain tumor cells, it is a primary target for the development of antiviral and anticancer therapies, including small-molecule inverse agonists and nanobodies (PMID: 23408461).

Other names

HCMV US28pUS28G protein-coupled receptor US28US28 vGPCRCytomegalovirus US28

Inhibition of constitutive signaling via inverse agonism, blockade of chemokine binding through antagonism, or targeted delivery of cytotoxins via ligand-mediated internalization.