Infection by porcine endogenous retrovirus after islet xenotransplantation in SCID mice
Infection by porcine endogenous retrovirus after islet xenotransplantation in SCID mice
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DOI：
10.1038/35024089
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发表时间：
2000-09-07
期刊：
影响因子：
64.8
通讯作者：
Salomon, DR
中科院分区：
文献类型：
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作者：
van der Laan, LJW;Lockey, C;Salomon, DR
猪等动物捐赠者可以为移植提供另一种器官来源。然而，异种移植的前景被可能的跨物种感染的公共健康风险所抵消(1，2)。所有的猪都含有多个副本的猪内源性逆转录病毒(PERV)(3，4)，通过共培养、感染性和伪分型实验(3，5-7)，至少有三种PERV变异体可以感染体外培养的人细胞系。因此，如果猪组织的异种移植导致PERV病毒复制，则存在将这种逆转录病毒传播和适应到人类宿主的风险。与PERV相关的C型逆转录病毒与其自然宿主中的造血系细胞的恶性肿瘤有关(8)。在这里，我们展示了猪胰岛产生PERV，并能在培养中感染人类细胞。在移植到NOD/SCID(非肥胖糖尿病，严重联合免疫缺陷)小鼠后，我们检测到正在进行的病毒表达，几个组织间隔被感染。这是猪组织移植后PERV在体内具有转录活性和跨物种感染性的首次证据。这些结果表明，在免疫抑制的人类患者中进行猪胰岛异种移植相关的PERV感染风险的担忧可能是合理的。
Animal donors such as pigs could provide an alternative source of organs for transplantation. However, the promise of xenotransplantation is offset by the possible public health risk of a cross-species infection(1,2). All pigs contain several copies of porcine endogenous retroviruses (PERV)(3,4), and at least three variants of PERV can infect human cell lines in vitro in co-culture, infectivity and pseudotyping experiments(3,5-7). Thus, if xenotransplantation of pig tissues results in PERV viral replication, there is a risk of spreading and adaptation of this retrovirus to the human host. C-type retroviruses related to PERV are associated with malignancies of haematopoietic lineage cells in their natural hosts(8). Here we show that pig pancreatic islets produce PERV and can infect human cells in culture. After transplantation into NOD/SCID (non-obese diabetic, severe combined immunodeficiency) mice, we detect ongoing viral expression and several tissue compartments become infected. This is the first evidence that PERV is transcriptionally active and infectious cross-species in vivo after transplantation of pig tissues. These results show that a concern for PERV infection risk associated with pig islet xenotransplantation in immunosuppressed human patients may be justified.