Efficient uptake of blood-borne BK and JC polyomavirus-like particles in endothelial cells of liver sinusoids and renal vasa recta.
Liver sinusoidal endothelial cells (LSECs) are specialized scavenger cells that mediate high-capacity clearance of soluble waste macromolecules and colloid material, including blood-borne adenovirus. To explore if LSECs function as a sink for other viruses in blood, we studied the fate of virus-like particles (VLPs) of two ubiquitous human DNA viruses, BK and JC polyomavirus, in mice. Like complete virions, VLPs specifically bind to receptors and enter cells, but unlike complete virions, they cannot replicate. 125I-labeled VLPs were used to assess blood decay, organ-, and hepatocellular distribution of ligand, and non-labeled VLPs to examine cellular uptake by immunohisto- and -cytochemistry. BK- and JC-VLPs rapidly distributed to liver, with lesser uptake in kidney and spleen. Liver uptake was predominantly in LSECs. Blood half-life (∼1 min), and tissue distribution of JC-VLPs and two JC-VLP-mutants (L55F and S269F) that lack sialic acid binding affinity, were similar, indicating involvement of non-sialic acid receptors in cellular uptake. Liver uptake was not mediated by scavenger receptors. In spleen, the VLPs localized to the red pulp marginal zone reticuloendothelium, and in kidney to the endothelial lining of vasa recta segments, and the transitional epithelium of renal pelvis. Most VLP-positive vessels in renal medulla did not express PV-1/Meca 32, suggesting location to the non-fenestrated part of vasa recta. The endothelial cells of these vessels also efficiently endocytosed a scavenger receptor ligand, formaldehyde-denatured albumin, suggesting high endocytic activity compared to other renal endothelia. We conclude that LSECs very effectively cleared a large fraction of blood-borne BK- and JC-VLPs, indicating a central role of these cells in early removal of polyomavirus from the circulation. In addition, we report the novel finding that a subpopulation of endothelial cells in kidney, the main organ of polyomavirus persistence, showed selective and rapid uptake of VLPs, suggesting a role in viremic organ tropism.
Department of Medical Biology, UiT - The Arctic University of Norway, Tromsø, Norway.
Jaione
J
Simon-Santamaria
Department of Microbiology and Infection Control, University Hospital of North Norway, Tromsø, Norway; Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway.
Christine Hanssen
CH
Rinaldo
Department of Biomedicine, University of Basel, Basel, Switzerland.
Piotr
P
Kardas
Department of Medical Biology, UiT - The Arctic University of Norway, Tromsø, Norway.
Ruomei
R
Li
Department of Medical Biology, UiT - The Arctic University of Norway, Tromsø, Norway.
Ivana
I
Malovic
Department of Medical Biology, UiT - The Arctic University of Norway, Tromsø, Norway.
Kjetil
K
Elvevold
Department of Medical Biology, UiT - The Arctic University of Norway, Tromsø, Norway.
Peter
P
McCourt
Department of Medical Biology, UiT - The Arctic University of Norway, Tromsø, Norway.
Bård
B
Smedsrød
Department of Biomedicine, University of Basel, Basel, Switzerland; Divisions of Infectious Diseases and Hospital Epidemiology, University Hospital of Basel, Basel, Switzerland.
Hans H
HH
Hirsch
Department of Medical Biology, UiT - The Arctic University of Norway, Tromsø, Norway.
Karen Kristine
KK
Sørensen
D000818:Animals; D001739:BK Virus / Q000378:metabolism; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000821:virology; D007577:JC Virus / Q000378:metabolism; D007668:Kidney / Q000098:blood supply* / Q000821:virology*; D008099:Liver / Q000166:cytology / Q000821:virology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D014771:Virion / Q000737:chemistry / Q000502:physiology*
D019158:N-Acetylneuraminic Acid