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原代猪内皮细胞对猪内源性逆转录病毒的表达及对人细胞的感染

Expression of pig endogenous retrovirus by primary porcine endothelial cells and infection of human cells.

作者信息

Martin U, Kiessig V, Blusch J H, Haverich A, von der Helm K, Herden T, Steinhoff G

机构信息

Leibniz Research Laboratories for Biotechnology and Artificial Organs, Hannover Medical School, Germany.

出版信息

Lancet. 1998 Aug 29;352(9129):692-4. doi: 10.1016/S0140-6736(98)07144-X.

DOI:10.1016/S0140-6736(98)07144-X
PMID:9728985
Abstract

BACKGROUND

The risk of interspecies transmission of retroviruses during xenotransplantation is suggested by reports of pig endogenous retrovirus (PERV) released from porcine cell lines productively infecting human cell lines in vitro and of infectious PERV being released from pig peripheral blood mononuclear cells after mitogenic stimulation. Endothelial cells are the main interface between a xenograft and the recipient's leucocytes and tissues.

METHODS

We have analysed pig primary aortic endothelial cells (PAEC) together with other transplantation-relevant porcine cells and tissues for expression of PERV mRNA. Release of virus particles by PAEC was monitored by reverse transcriptase (RT) activity in the medium of cultured PAEC. Infectivity for human cells was tested by co-cultivation of irradiated PAEC with the human embryonal kidney cell line HEK293 and looking for virus release from the human cells.

FINDINGS

PAECs, hepatocytes, lung, and skin from a variety of pig strains and breeds expressed PERV mRNA. PAEC released infectious particles. Co-cultivation of PAEC and HEK293 led to productive infection of the human cells and expression of PERV types A and B.

INTERPRETATION

Release of infectious virus from PAEC occurred without mitogenic stimulation, suggesting a serious risk of retrovirus transfer after xenotransplantation.

摘要

背景

猪内源性逆转录病毒(PERV)可从猪细胞系中释放出来,在体外有效感染人细胞系,且有丝分裂原刺激后猪外周血单个核细胞可释放有传染性的PERV,这些报道提示了异种移植过程中逆转录病毒跨物种传播的风险。内皮细胞是异种移植物与受体白细胞及组织之间的主要界面。

方法

我们分析了猪原代主动脉内皮细胞(PAEC)以及其他与移植相关的猪细胞和组织中PERV mRNA的表达情况。通过培养的PAEC培养基中的逆转录酶(RT)活性监测PAEC释放病毒颗粒的情况。通过将经辐照的PAEC与人胚肾细胞系HEK293共培养,并观察人细胞中病毒的释放情况,来检测对人细胞的感染性。

结果

来自多种猪品系和品种的PAEC、肝细胞、肺和皮肤均表达PERV mRNA。PAEC释放出有传染性的颗粒。PAEC与HEK293共培养导致人细胞发生有效感染,并表达A和B型PERV。

解读

PAEC在无有丝分裂原刺激的情况下释放出有传染性的病毒,提示异种移植后逆转录病毒转移存在严重风险。

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