Yu P, Zhang L, Li S, Li Y, Cheng J, Lu Y, Zeng Y, Bu H
Laboratory of Transplant Engineering and Immunology, Departmentment of Pathology, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
Transplant Proc. 2004 Oct;36(8):2485-7. doi: 10.1016/j.transproceed.2004.07.055.
Pigs have been the most likely animal as the source of cells, tissues, and organs for xenotransplantation. But the use of pigs in xenotransplantation is associated with the risk of porcine endogenous retrovirus (PERV) transmission. Previous studies have identified that the proviruses are integrated into the genome of normal pigs and that virus particles released from the porcine cells can infect human cells in vitro. As a unique inbred pig, Banna minipig inbred (BMI) has a huge potential value for xenotransplantation and medical research. It has been the focal experimental animal for pig-to-human xenotransplantation in China, due to its clear genetic background and tiny individual differences. To evaluate whether the potential risk of PERV exists in inbred pigs, a series of screening experiments were performed herein. The results of PCR with primers specific for gag, pol, and env showed that proviruses existed in the genome of BMI, and the PERV subtypes were PERV-A and PERV-B. PERV mRNA was expressed functionally in BMI. Positive results of an RT assay identified that PERV in BMI had potential infectivity, but the concentration of PERV reverse transcriptase in BMI was almost 20 times lower than that of HIV. These results suggested that gag, pol and env genes of PERV were not lost during inbreeding, which created favorable conditions to produce viral particles that could possibly infect human cells in xenotransplantation.
猪一直是异种移植中细胞、组织和器官最有可能的来源动物。但在异种移植中使用猪与猪内源性逆转录病毒(PERV)传播的风险相关。先前的研究已确定,前病毒整合到正常猪的基因组中,并且从猪细胞释放的病毒颗粒在体外可感染人类细胞。作为一种独特的近交系猪,版纳微型猪近交系(BMI)在异种移植和医学研究中具有巨大的潜在价值。由于其清晰的遗传背景和微小的个体差异,它一直是中国猪到人异种移植的重点实验动物。为了评估近交系猪中是否存在PERV的潜在风险,本文进行了一系列筛选实验。用针对gag、pol和env的特异性引物进行PCR的结果表明,前病毒存在于BMI的基因组中,PERV亚型为PERV - A和PERV - B。PERV mRNA在BMI中功能性表达。逆转录试验的阳性结果表明,BMI中的PERV具有潜在传染性,但BMI中PERV逆转录酶的浓度几乎比HIV低20倍。这些结果表明,PERV的gag、pol和env基因在近交过程中并未丢失,这为产生可能在异种移植中感染人类细胞的病毒颗粒创造了有利条件。