PERV Free Swine for Xenotransplantation

描述（由申请人提供）：需要移植的患者人数与可用的器官捐献者人数之间存在巨大差距。猪可以很容易地解决未满足的需求。许多组织的生理学与人类的生理学接近。它们可以在清洁的受控条件下饲养。然而，一个潜在的缺点是在猪基因组中定义的病毒，PERV。在与人细胞系的组织共培养中，PERV可被传递至人细胞。尚未在人类或动物模型中证明任何感染或致病状态。PERV由三种病毒组成：PERV A、PERV B和PERV C。PERV A和PERV C是传播到人类细胞系的罪魁祸首。我们的项目已经维持了一群非常干净的猪，用于潜在的临床异种移植。用我们的猪的肝细胞进行的共培养试验未能将病毒传给人类细胞。对猪进行筛查，它们是PERV C阴性。大多数人是阴性的。一头猪对所有三种病毒以及PERV的通用gag/pol基因均为阴性。该应用将产生一群无PERV的猪。将通过病毒学方法对这些猪进行彻底的PERV评价。作为可能感染性的严格试验，将在无PERV猪的子宫内培养人细胞。公共卫生相关性猪器官移植在解决人类器官捐献者严重短缺问题方面可能很有价值。一些器官，例如心脏和胰岛，在生理上与人类非常相似。此外，猪可以在非常清洁的受控条件下饲养。然而，猪内源性逆转录病毒（PERV）引起了人们的关注。PERV是猪的DNA的一部分，因此它不能通过常规手段根除。我们为临床异种移植而饲养的一个牛群发现PERV非常少。一只猪似乎是自由的。该申请将产生用于临床异种移植的无PERV猪群。

DESCRIPTION (provided by applicant): There is a huge disparity between the number of patients who need a transplant and the available organ donors. Pigs could readily resolve the unmet need. The physiology of many tissues is close to that of humans. They can be raised in clean controlled conditions. One potential drawback, however, is a virus defined in the porcine genome, PERV. In tissue co-culture with human cell lines, PERV may be transmitted to the human cells. There has not yet been demonstrated any infectious or pathogenic state in humans or animal models. PERV consists of three viruses: PERV A, PERV B and PERV C. PERV A and PERV C are the primary culprits for transmission to human cell lines. Our program has maintained a herd of very clean pigs for potential clinical xenotransplantation. Co-culture tests with liver cells from our pigs failed to pass the virus to human cells. Screening the pigs, they are PERV C negative. The majority are PERV A negative. One pig is negative for all three viruses as well as the generic gag/pol gene for PERV. This application will generate a herd of PERV free pigs. These pigs will be thoroughly evaluated for PERV by virologic methods. As a stringent test for possible infectivity, human cells will be cultured in utero in PERV free pigs. PUBLIC HEALTH RELEVANCE Organ transplants from pigs could be valuable in resolving the severe shortage of human organ donors. Some organs, such as hearts and pancreatic islets, are physiologically very similar to humans. Furthermore, pigs can be raised under very clean controlled conditions. However, concern has been raised about a virus present in pigs, porcine endogenous retrovirus (PERV). PERV is part of the DNA of the pig, so it cannot be eradicated by conventional means. A herd that has been maintained by us for clinical xenotransplantation has been found to have very little PERV. One pig appears to be PERV free. This application would produce a PERV free swine herd for clinical xenotransplantation.