Yoo D, Giulivi A
Department of Pathobiology, Ontario Veterinary College, University of Guelph.
Can J Vet Res. 2000 Oct;64(4):193-203.
The clinical success of allotransplantation and the shortage of donor organs have led to a proposal for the use of animal organs as alternative therapeutic materials for humans. In that regard, swine are preferable to non-human primates as a source of donor organs. While applications for clinical trials for xenotransplantation have not yet been received in Canada, several trials have already been authorized in the United States. A major concern, however, is the potential for xenogeneic transmission of viruses from animals to humans via organ, tissue, or cellular transplantation or via ex vivo exposure of humans to porcine biologic materials. Xenotransplantation allows viruses to bypass the normal immunological defense mechanisms of the recipient. Furthermore, the use of immunosuppressive drugs following transplantation may facilitate the xenogeneic transmission of zoonotic agents. Of porcine viruses, swine hepatitis E virus does not cause any clinical symptoms in the natural host but is a likely zoonotic agent that can infect humans and cause hepatitis. Porcine circovirus type 1 is prevalent in swine populations with no known association with clinical disease, while circovirus type 2 causes post-weaning multi-systemic wasting syndrome. Porcine endogenous retrovirus is integrated into the host chromosomes while porcine cytomegalovirus undergoes latent infection. Two additional porcine herpesviruses have recently been identified in swine and have been named porcine lymphotrophic herpesviruses. These herpesviruses can potentially become reactivated in human recipients after xenotransplantation. All in all, there are a number of viruses in swine that are of primary concern to screen and eliminate from xenotransplantation protocols. Epidemiology and the current knowledge on xenogeneic risk of these viruses are discussed.
同种异体移植的临床成功以及供体器官的短缺,引发了关于使用动物器官作为人类替代治疗材料的提议。在这方面,猪作为供体器官来源比非人灵长类动物更具优势。虽然加拿大尚未收到异种移植临床试验的申请,但美国已经批准了几项试验。然而,一个主要问题是病毒通过器官、组织或细胞移植,或通过人类在体外接触猪生物材料,从动物向人类异种传播的可能性。异种移植使病毒能够绕过受体的正常免疫防御机制。此外,移植后使用免疫抑制药物可能会促进人畜共患病原体的异种传播。在猪病毒中,猪戊型肝炎病毒在自然宿主中不会引起任何临床症状,但它很可能是人畜共患病原体,可感染人类并导致肝炎。猪圆环病毒1型在猪群中普遍存在,与已知临床疾病无关联,而2型圆环病毒会导致断奶后多系统消耗综合征。猪内源性逆转录病毒整合到宿主染色体中,而猪巨细胞病毒会发生潜伏感染。最近在猪中又鉴定出另外两种猪疱疹病毒,并将其命名为猪嗜淋巴细胞疱疹病毒。这些疱疹病毒在异种移植后可能会在人类受体中重新激活。总而言之,猪中有许多病毒是异种移植方案中需要重点筛查和消除的对象。本文讨论了这些病毒的流行病学以及当前关于异种风险的认识。