PERV data renew xeno debate
PERV data renew xeno debate
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DOI：
10.1038/80207
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发表时间：
2000-10
影响因子：
46.9
通讯作者：
E. Dorey
中科院分区：
文献类型：
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作者：
E. Dorey
PPL Therapeutics （Roslin， UK）的分析研究同意Fishman的观点。科尔曼说：“这是一个模型，但它是一个很难推断的模型。”他解释说，目前还不清楚传染性是否已经扩散到老鼠细胞，而不仅仅是在猪细胞中，这些细胞已经进入了不同的器官。他说：“有一种可能性是，他们检测的是最初植入这些动物体内的细胞残留物。”他解释说，完全免疫受损的小鼠不会像正常小鼠那样排斥外来组织。然而，尽管有几家公司正在研究敲除α- 1,3 -半乳糖转移酶基因，这样猪的器官就不会引起人类的急性排斥反应，但患者仍然需要使用免疫抑制剂来避免慢性排斥反应——这将增加患者患逆转录病毒的风险。然而，所罗门的发现可能并不像最初看起来那么令人沮丧，因为正如所罗门自己指出的那样，尽管这些老鼠患有严重的联合免疫缺陷（SCID），但它们并没有生病，也没有任何活跃病毒传播的证据。“我们所有的数据都表明，到2个月的时间点，病毒已经处于潜伏状态。”Fishman指出，在任何情况下，从猪到老鼠的传播都不是问题。“我们可能会也可能不会感染人类或非人类灵长类动物，这一事实更接近令人担忧的领域。”针对PERV跨物种传播提出的解决方案之一是，在首先敲除或破坏关键的PERV基因后，使用克隆技术来产生无PERV的动物。生物移植公司的消息称，其一种近交迷你猪的外周血细胞不会传播在培养中感染人类细胞的PERV A或B-2变体，这似乎增加了这一说法的可信度，尽管这种猪是用传统育种方法生产的。虽然原始数据尚未在同行评议的期刊上发表，但所罗门对他们的建议充满热情。他说：“科学影响远远超出了该公司意外拥有这头猪的事实。”生物移植公司的首席科学官茱莉亚·格林斯坦说，理性地敲门
ANALYSIS research at PPL Therapeutics (Roslin, UK) agrees with Fishman.“It is a model, but it’sa very difficult model to extrapolate from,” says Colman. He explains that it’s not clear that the infectivity had spread to mouse cells and was not just in the pig cells that had entered various organs.“There’sa possibility that what they were assaying was the remnants of the cells that they originally put in those animals,” he says, explaining that completely immunocompromised mice wouldn’t reject foreign tissue in the way a normal mouse would. However, although several companies are working on knocking out the α-1, 3-galactosyl transferase gene so that pig organs don’t prompt acute rejection in humans, patients would still need to be put on immunosuppressives to avoid chronic rejection—something that puts the patient at an increased risk for the development of retroviruses. Nevertheless, Salomon’s findings may not be as discouraging as they first seem because, as Salomon himself points out, even though the mice are severe combined immunodeficient (SCID) they are not sick and there was no evidence for any kind of active viral spread.“All our data suggests is that by the 2 month time point, the virus had already become latent.” In any case, transmission from pigs to mice is a bit of a non-issue, points out Fishman.“The fact that we may or may not be able to infect humans or non-human primates is much closer to the area of concern.” One of the proposed solutions to crossspecies PERV transmission is that cloning be used to generate PERV-free animals after first knocking out or disrupting crucial PERV genes. BioTransplant’s news that peripheral blood cells from one of its line of in-bred mini-swine don’t transmit PERV A or B—2 variants that infect human cells in culture—seems to add credence to this, even though the swine were produced by traditional breeding methods. Although the primary data has yet to be published in a peerreviewed journal, Salomon is enthusiastic about what they suggest.“The scientific impact is way, way beyond the fact that the company accidentally has this pig,” he says. BioTransplant’s chief scientific officer Julia Greenstein says that rationally knocking