Exosomal release of the virus-encoded chemokine receptor US28 contributes to chemokine scavenging

Maarten P. Bebelman, Irfan M. Setiawan, Nick D. Bergkamp, Jeffrey R. van Senten, Caitrin Crudden, Jan Paul M. Bebelman, Frederik J. Verweij, Guillaume van Niel, Marco Siderius, D. Michiel Pegtel, Martine J. Smit

Research output: Contribution to journalArticleAcademicpeer-review


The human cytomegalovirus (HCMV)-encoded chemokine receptor US28 contributes to various aspects of the viral life cycle and promotes immune evasion by scavenging chemokines from the microenvironment of HCMV-infected cells. In contrast to the plasma membrane localization of most human chemokine receptors, US28 has a predominant intracellular localization. In this study, we used immunofluorescence and electron microscopy to determine the localization of US28 upon exogenous expression, as well as in HCMV-infected cells. We observed that US28 localizes to late endosomal compartments called multivesicular bodies (MVBs), where it is sorted in intraluminal vesicles. Live-cell total internal reflection fluorescence (TIRF) microscopy revealed that US28-containing MVBs can fuse with the plasma membrane, resulting in the secretion of US28 on exosomes. Exosomal US28 binds the chemokines CX3CL1 and CCL5, and US28-containing exosomes inhibited the CX3CL1-CX3CR1 signaling axis. These findings suggest that exosomal release of US28 contributes to chemokine scavenging and immune evasion by HCMV.
Original languageEnglish
Article number107412
Pages (from-to)1-16
Number of pages17
Issue number8
Early online date18 Jul 2023
Publication statusPublished - 18 Aug 2023


  • Cell biology
  • Immunology

Cite this