Mueller Nicolas J, Barth Rolf N, Yamamoto Shin, Kitamura Hiroshi, Patience Clive, Yamada Kazuhiko, Cooper David K C, Sachs David H, Kaur Amitinder, Fishman Jay A
Infectious Diseases Division, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
J Virol. 2002 May;76(10):4734-40. doi: 10.1128/jvi.76.10.4734-4740.2002.
Xenotransplantation of porcine organs carries the risk of reactivation of latent virus in donor and recipient tissues as well as transmission of viruses between species. We have investigated the activation of baboon cytomegalovirus (BCMV) and porcine CMV (PCMV) in a pig-to-primate model of xenotransplantation. Tissues originating from a series of six swine-to-baboon composite thymokidney xenotransplants were investigated. Four immunosuppressed baboons died (survival range, 7 to 27 days) with the graft in situ. Increases in BCMV DNA copy numbers occurred in three (75%) of these baboons and was thought to be responsible for pneumonitis and the death of one animal. In two baboons, disseminated intravascular coagulation was successfully treated by graftectomy and discontinuation of immunosuppression. PCMV was upregulated in five of six xenografts (83%). PCMV infection was associated with ureteric necrosis in one xenograft. Although significantly increased in native tissues, low levels of BCMV and PCMV were also detected in tissues other than that of the native viral host species. The cross-species presence of CMV did not appear to cause clinical or histological signs of invasive disease. Thus, viral infections with clinical disease were restricted to tissues of the native species of each virus. Intensive immune suppression currently required for xenotransplantation results in a significant risk of reactivation of latent infections by BCMV and PCMV. It is not yet known whether viral DNA detected across species lines represents cellular microchimerism, ongoing viral infection, or uptake of free virus. The observation of graft injury by PCMV demonstrates that CMV will be an important pathogen in immunosuppressed xenograft recipients. Strategies must be developed to exclude CMV from porcine organ donors.
猪器官的异种移植存在供体和受体组织中潜伏病毒重新激活以及病毒跨物种传播的风险。我们在猪到灵长类动物的异种移植模型中研究了狒狒巨细胞病毒（BCMV）和猪巨细胞病毒（PCMV）的激活情况。对来自一系列六例猪到狒狒复合胸腺肾异种移植的组织进行了研究。四只免疫抑制的狒狒在移植物原位的情况下死亡（存活时间为7至27天）。其中三只（75%）狒狒的BCMV DNA拷贝数增加，被认为是导致肺炎和一只动物死亡的原因。在两只狒狒中，通过切除移植物和停止免疫抑制成功治疗了弥散性血管内凝血。六例异种移植中有五例（83%）PCMV上调。PCMV感染与一例异种移植中的输尿管坏死有关。尽管在天然组织中显著增加，但在天然病毒宿主物种以外的组织中也检测到了低水平的BCMV和PCMV。巨细胞病毒的跨物种存在似乎并未引起侵袭性疾病的临床或组织学迹象。因此，伴有临床疾病的病毒感染仅限于每种病毒的天然物种的组织。目前异种移植所需的强化免疫抑制导致BCMV和PCMV潜伏感染重新激活的重大风险。目前尚不清楚跨物种检测到的病毒DNA是代表细胞微嵌合体、持续的病毒感染还是游离病毒的摄取。PCMV对移植物损伤的观察表明，巨细胞病毒将是免疫抑制的异种移植受者中的一种重要病原体。必须制定策略以从猪器官供体中排除巨细胞病毒。
