Switzer W M, Michler R E, Shanmugam V, Matthews A, Hussain A I, Wright A, Sandstrom P, Chapman L E, Weber C, Safley S, Denny R R, Navarro A, Evans V, Norin A J, Kwiatkowski P, Heneine W
Division of AIDS, STDs, and TB Research Laboratory, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
Transplantation. 2001 Apr 15;71(7):959-65. doi: 10.1097/00007890-200104150-00022.
Nonhuman primates (NHPs) have been widely used in different porcine xenograft procedures inevitably resulting in exposure to porcine endogenous retrovirus (PERV). Surveillance for PERV infection in these NHPs may provide information on the risks of cross-species transmission of PERV, particularly for recipients of vascularized organ xenografts for whom data from human clinical trials is unavailable.
We tested 21 Old World and 2 New World primates exposed to a variety of porcine xenografts for evidence of PERV infection. These NHPs included six baboon recipients of pig hearts, six bonnet macaque recipients of transgenic pig skin grafts, and nine rhesus macaque and two capuchin recipients of encapsulated pig islet cells. Serologic screening for PERV antibody was done by a validated Western blot assay, and molecular detection of PERV sequences in peripheral blood mononuclear cells (PBMCs) and plasma was performed using sensitive polymerase chain reaction and reverse transcriptase-polymerase chain reaction assays, respectively. Spleen and lymph node tissues available from six bonnet macaques and three rhesus macaques were also tested for PERV sequences.
All plasma samples were negative for PERV RNA suggesting the absence of viremia in these xenografted animals. Similarly, PERV sequences were not detectable in any PBMC and tissue samples, arguing for the lack of latent infection of these compartments. In addition, all plasma samples were negative for PERV antibodies.
These data suggest the absence of PERV infection in all 23 NHPs despite exposure to vascularized porcine organs or tissue xenografts and the use of immunosuppressive therapies in some animals. These findings suggest that PERV is not easily transmitted to these NHP species through these types of xenografts.
非人灵长类动物(NHPs)已广泛应用于不同的猪异种移植程序中,不可避免地导致接触猪内源性逆转录病毒(PERV)。监测这些非人灵长类动物中的PERV感染情况,可能会提供有关PERV跨物种传播风险的信息,特别是对于接受血管化器官异种移植的患者,目前尚无来自人类临床试验的数据。
我们检测了21只旧世界灵长类动物和2只新世界灵长类动物,这些动物接触过各种猪异种移植物,以寻找PERV感染的证据。这些非人灵长类动物包括6只接受猪心脏移植的狒狒、6只接受转基因猪皮肤移植的冠毛猕猴,以及9只接受封装猪胰岛细胞移植的恒河猴和2只卷尾猴。通过经过验证的蛋白质印迹法进行PERV抗体的血清学筛查,并分别使用灵敏的聚合酶链反应和逆转录聚合酶链反应检测外周血单核细胞(PBMC)和血浆中的PERV序列。还对6只冠毛猕猴和3只恒河猴的脾脏和淋巴结组织进行了PERV序列检测。
所有血浆样本的PERV RNA均为阴性,表明这些异种移植动物不存在病毒血症。同样,在任何PBMC和组织样本中均未检测到PERV序列,这表明这些部位不存在潜伏感染。此外,所有血浆样本的PERV抗体均为阴性。
这些数据表明,尽管23只非人灵长类动物接触过血管化猪器官或组织异种移植物,且部分动物使用了免疫抑制疗法,但所有动物均未感染PERV。这些发现表明,PERV不容易通过这些类型的异种移植传播给这些非人灵长类动物物种。