Denner Joachim, Specke Volker, Karlas Alexander, Chodnevskaja Irina, Meyer Thomas, Moskalenko Vasiliy, Kurth Reinhard, Ulrichs Karin
Robert Koch Institute, Berlin, Germany.
Ann Transplant. 2008;13(1):20-31.
Xenotransplantation from pig to humans may be associated with the risk of transmission of porcine endogenous retroviruses (PERVs) that are present in the genome of all pigs and that infect human cells in vitro. However, it remains unclear whether PERVs infect transplant recipients in vivo and, if so, whether they are pathogenic. It is therefore essential to perform in vivo infection studies in animal models.
MATERIAL/METHODS: To study PERV transmission in rats, rat primary cells and cell lines were treated in vitro with virus from different sources. Based on the assumption that susceptible cell lineages not yet tested in vitro could be present in the animal, PERV was inoculated into naïve and immunosuppressed animals. To investigate PERV transmission in a long-term exposure experiment, sera from animals grafted with pig Langerhans islet cells were tested in a Western blot assay for antibodies against PERVs. The animals were treated with streptozotocin to induce diabetes and microencapsulated and non-microencapsulated pig islet cells were applied without immunosuppression.
No productive infection of a few selected rat primary cells or cell lines was observed in vitro. PERV-specific antibodies were found in none of the animals and no integration of PERV into rat cells of different organs was observed, indicating that infection had not occurred.
This report demonstrates a lack of infection of rats in vivo even during immunosuppression or long-term exposure (up to 460 days) to a functioning xenotransplant. This report also shows that rats possibly due to a low receptor concentration on their cells are not a suitable animal model to study PERV transmission in vivo.
从猪到人的异种移植可能与猪内源性逆转录病毒（PERVs）传播的风险相关，PERVs存在于所有猪的基因组中，并且在体外可感染人类细胞。然而，目前尚不清楚PERVs在体内是否感染移植受者，如果感染，它们是否具有致病性。因此，在动物模型中进行体内感染研究至关重要。
材料/方法：为了研究大鼠体内的PERV传播，用来自不同来源的病毒在体外处理大鼠原代细胞和细胞系。基于动物体内可能存在尚未在体外测试的易感细胞谱系这一假设，将PERV接种到未接触过病原体的和免疫抑制的动物体内。为了在长期暴露实验中研究PERV传播，对移植了猪朗格汉斯胰岛细胞的动物血清进行蛋白质印迹分析，检测抗PERVs抗体。用链脲佐菌素处理动物以诱导糖尿病，然后在不进行免疫抑制的情况下应用微囊化和非微囊化的猪胰岛细胞。
在体外未观察到少数选定的大鼠原代细胞或细胞系发生有效感染。在所有动物中均未发现PERV特异性抗体，也未观察到PERV整合到不同器官的大鼠细胞中，表明未发生感染。
本报告表明，即使在免疫抑制或长期暴露（长达460天）于有功能的异种移植的情况下，大鼠在体内也未发生感染。本报告还表明，大鼠可能由于其细胞上受体浓度较低，不是研究体内PERV传播的合适动物模型。
