HCMV-encoded chemokine receptor US28 employs multiple routes for internalization.

The human cytomegalovirus-encoded G protein-coupled receptor homologue US28 binds inflammatory chemokines and sequesters them from the environment of infected cells. Low surface deposition and endocytosis are dependent on constitutive C-terminal phosphorylation, suggesting a requirement for beta-arrestin binding in receptor internalization. In this report, a US28-dependent redistribution of beta-arrestin into vesicular structures occurred, although internalization of US28 was independent of beta-arrestin.

Surface expression and endocytosis of the human cytomegalovirus-encoded chemokine receptor US28 is regulated by agonist-independent phosphorylation.

Human cytomegalovirus encodes the G protein-coupled chemokine receptor homologue US28 that binds several CC chemokines and sequesters extracellular chemokines from the environment of infected cells. Mechanistically, it has been shown that US28 undergoes rapid constitutive receptor endocytosis and recycling. Monoclonal antibodies were raised that allowed the characterization of a ligand-independent phosphorylation and low surface expression of the US28 receptor in transiently transfected HEK293A cells.

Inhibition of metalloproteinases enhances the internalization of anti-CD30 antibody Ki-3 and the cytotoxic activity of Ki-3 immunotoxin.

CD30 is selectively expressed on the tumor cells of a variety of malignant disorders of the immune system and can therefore be used as a target for an anti-CD30 antibody-based immunotherapy. However, CD30 is cleaved at the cell surface by tumor necrosis factor-alpha converting enzyme (TACE). This metalloproteinase releases the soluble ectodomain of CD30 (sCD30), which is able to neutralize immunotherapeutic agents before these reach their target cells.