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揭示内皮细胞在巨细胞病毒传播中难以捉摸的作用。

Shedding light on the elusive role of endothelial cells in cytomegalovirus dissemination.

机构信息

Max von Pettenkofer-Institute, Ludwig Maximilians-University, Munich, Germany.

出版信息

PLoS Pathog. 2011 Nov;7(11):e1002366. doi: 10.1371/journal.ppat.1002366. Epub 2011 Nov 17.

DOI:10.1371/journal.ppat.1002366
PMID:22114552
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3219709/
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-naïve 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 poorly spread to recipient tissues. Similarly, in reverse direction, EC-derived virus from infected Tie2-cre(+) recipient tissues poorly spread to the transplant. These data contradict any privileged role of EC in CMV dissemination and challenge an indiscriminate applicability of the primary and secondary viremia concept of virus dissemination.

摘要

巨细胞病毒(CMV)通常通过实体器官移植传播,并与移植物失功有关。内皮细胞(EC)形成循环系统和器官实质之间的边界,适合病毒在移植过程中双向传播。我们应用 Cre/loxP 介导的 EC 源性小鼠 CMV(MCMV)的绿色荧光标记来定量感染的 EC 在小鼠模型中移植相关 CMV 传播中的作用。源自受感染的 Tie2-cre(+)心脏和肾脏移植的 EC 源性和非 EC 源性病毒均可通过原发性病毒血症轻易传播给 MCMV 未感染的受体。相比之下,当受感染的受体中通过原发性病毒血症感染 Tie2-cre(+)移植时,重组的 EC 源性病毒很少传播到受者组织。同样,相反,来自受感染的 Tie2-cre(+)受者组织的 EC 源性病毒很少传播到移植部位。这些数据与 EC 在 CMV 传播中具有特权作用的观点相矛盾,并挑战了病毒传播的原发性和继发性病毒血症概念的普遍适用性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/faf8/3219709/4abe22260dd9/ppat.1002366.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/faf8/3219709/dabcd04ab2c5/ppat.1002366.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/faf8/3219709/caa61a6675bb/ppat.1002366.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/faf8/3219709/6a4a64b0c107/ppat.1002366.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/faf8/3219709/7ae15515fde5/ppat.1002366.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/faf8/3219709/4abe22260dd9/ppat.1002366.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/faf8/3219709/dabcd04ab2c5/ppat.1002366.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/faf8/3219709/caa61a6675bb/ppat.1002366.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/faf8/3219709/6a4a64b0c107/ppat.1002366.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/faf8/3219709/7ae15515fde5/ppat.1002366.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/faf8/3219709/4abe22260dd9/ppat.1002366.g005.jpg

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Murine cytomegalovirus displays selective infection of cells within hours after systemic administration.
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