Human Cytomegalovirus-Encoded Receptor US28 Is Expressed in Renal Allografts and Facilitates Viral Spreading In VitroLollinga, W. T., de Wit, R. H., Rahbar, A., Vasse, G. F., Davoudi, B., Diepstra, A., Riezebos-Brilman, A., Harmsen, M. C., Hillebrands, J-L., Soderberg-Naucler, C., van Son, W. J., Smit, M. J., Sanders, J-S. & van den Born, J., Mar-2017, In : Transplantation. 101, 3, p. 531-540 10 p.
Research output: Contribution to journal › Article › Academic › peer-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.
DISCUSSION: 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.
|Number of pages||10|
|Publication status||Published - Mar-2017|
- CHEMOKINE RECEPTOR, ENDOTHELIAL-CELLS, INFECTION, PROTEIN, REJECTION, PROMOTES, GRAFT, RECIPIENTS, DISEASE, IMPACT