Human cytomegalovirus-encoded receptor US28 is expressed in renal allografts and facilitates viral spreading in vitro.

Wouter T Lollinga, Raymond H de Wit, Afsar Rahbar, Gwenda F Vasse, Belghis Davoudi, Arjan Diepstra, Annelies Riezebos-Brilman, Martin C Harmsen, Jan-Luuk Hillebrands, Cecilia Söderberg-Naucler, Willem J van Son, Martine J Smit, Jan-Stephan Sanders, Jacob van den Born

Research output: Contribution to JournalArticleAcademicpeer-review


BACKGROUND: Renal transplantation is the preferred treatment for patients with end-stage renal disease. Human cytomegalovirus (HCMV) activation is associated with decreased renal graft function and survival. Human cytomegalovirus encodes several immune modulatory proteins, including the G protein-coupled receptor US28, which scavenges human chemokines and modulates intracellular signaling.

METHODS: Our aim was to identify the expression and localization of US28 in renal allograft biopsies by immunohistochemistry and determine its role in viral spreading in vitro.

RESULTS: Immunohistochemistry revealed US28 in 31 of 34 renal transplant biopsies from HCMV-seropositive donors. Expression was independent of HCMV viremia or IgG serostatus. US28 was predominantly expressed in the cytoplasm of vascular smooth muscle cells (VSMCs) and tubular epithelial cells, with a median positivity of 20% and 40%, respectively. Also, US28-positive cells were present within arterial neointima. In contrast to US28, HCMV-encoded immediate early antigen was detected in less than 5% of VSMCs, tubular epithelial cells, interstitial endothelium, interstitial inflammatory infiltrates, and glomerular cells.Primary VSMCs were infected with green fluorescent protein-tagged wild type or US28-deficient HCMV. The viral spreading of US28-deficient HCMV, via culture medium or cell-to-cell transmission, was significantly impeded as shown by green fluorescent protein (ie, infected) cell quantification and quantitative real-time polymerase chain reaction. Additionally, the number and size of foci was smaller.

CONCLUSIONS: In summary, HCMV-encoded US28 was detected in renal allografts from HCMV-positive donors independent of viremia and serostatus. Also, US28 facilitates HCMV spreading in VSMCs in vitro. Because the vasculature is affected in chronic renal transplant dysfunction, US28 may provide a potential target for therapeutic intervention.

Original languageEnglish
Pages (from-to)531-540
Number of pages10
Issue number3
Early online date1 Mar 2017
Publication statusPublished - Mar 2017

Bibliographical note

pmid 27362315


  • Adult
  • Aged
  • Allografts
  • Antibodies, Viral
  • Biomarkers
  • Biopsy
  • Cells, Cultured
  • Cytomegalovirus
  • Cytomegalovirus Infections
  • Epithelial Cells
  • Female
  • Humans
  • Immunoglobulin G
  • Immunohistochemistry
  • Journal Article
  • Kidney
  • Kidney Transplantation
  • Male
  • Middle Aged
  • Muscle, Smooth, Vascular
  • Myocytes, Smooth Muscle
  • Receptors, Chemokine
  • Retrospective Studies
  • Time Factors
  • Tissue Donors
  • Viral Proteins
  • Virulence
  • Young Adult


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