shedding light on the elusive role of endothelial cells in cytomegalovirus dissemination揭示了难以捉摸的内皮细胞在巨细胞病毒传播中的作用.pdfVIP

Shedding Light on the Elusive Role of Endothelial Cells in Cytomegalovirus Dissemination 1. 2. 2 ¨ 1 1 ¨ 3 Torsten Sacher , Joachim Andrassy , Aivars Kalnins , Lars Dolken , Stefan Jordan , Jurgen Podlech , 1 2 3 1 Zsolt Ruzsics , Karl-Walter Jauch , Matthias J. Reddehase , Ulrich H. Koszinowski * 1 Max von Pettenkofer-Institute, Ludwig Maximilians-University, Munich, Germany, 2 Surgery Department, Klinikum Großhadern, Ludwig Maximilians-University, Munich, Germany, 3 Institute for Virology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany Abstract Cytomegalovirus (CMV) is frequently transmitted by solid organ transplantation and is associated with graft failure. By forming the boundary between circulation and organ parenchyma, endothelial cells (EC) are suited for bidirectional virus spread from and to the transplant. We applied Cre/loxP-mediated green-fluorescence-tagging of EC-derived murine CMV (MCMV) to quantify the role of infected EC in transplantation-associated CMV dissemination in the mouse model. Both EC- and non-EC-derived virus originating from infected Tie2-cre+ heart and kidney transplants were readily transmitted to ¨ + MCMV-naıve recipients by primary viremia. In contrast, when a Tie2-cre transplant was infected by primary viremia in an infected recipient, the recombined EC-derived virus