Institut für Virologie, Freie Universität Berlin, 14163 Berlin, Germany.
Schubiomed Consultancy, 3583 VH Utrecht, The Netherlands.
Viruses. 2021 Sep 18;13(9):1869. doi: 10.3390/v13091869.
Minipigs play an important role in biomedical research and they have also been used as donor animals for preclinical xenotransplantations. Since zoonotic microorganisms including viruses can be transmitted when pig cells, tissues or organs are transplanted, virus safety is an important feature in xenotransplantation. Whereas most porcine viruses can be eliminated from pig herds by different strategies, this is not possible for porcine endogenous retroviruses (PERVs). PERVs are integrated in the genome of pigs and some of them release infectious particles able to infect human cells. Whereas PERV-A and PERV-B are present in all pigs and can infect cells from humans and other species, PERV-C is present in most, but not all pigs and infects only pig cells. Recombinant viruses between PERV-A and PERV-C have been found in some pigs; these recombinants infect human cells and are characterized by high replication rates. PERV-A/C recombinants have been found mainly in minipigs of different origin. The possible reasons of this high prevalence of PERV-A/C in minipigs, including inbreeding and higher numbers and expression of replication-competent PERV-C in these animals, are discussed in this review. Based on these data, it is highly recommended to use only pig donors in clinical xenotransplantation that are negative for PERV-C.
小型猪在生物医学研究中发挥着重要作用,它们也被用作临床前异种移植的供体动物。由于当猪的细胞、组织或器官被移植时,包括病毒在内的人畜共患微生物可以传播,因此病毒安全性是异种移植的一个重要特征。虽然大多数猪病毒可以通过不同的策略从猪群中消除,但这对于猪内源性逆转录病毒(PERVs)来说是不可能的。PERVs 整合在猪的基因组中,其中一些会释放出能够感染人类细胞的传染性颗粒。虽然 PERV-A 和 PERV-B 存在于所有猪中,并能感染来自人类和其他物种的细胞,但 PERV-C 存在于大多数猪中,但不是所有猪中,并且只感染猪细胞。在一些猪中发现了 PERV-A 和 PERV-C 之间的重组病毒;这些重组病毒感染人类细胞,其特点是复制率高。PERV-A/C 重组病毒主要存在于不同来源的小型猪中。本文讨论了小型猪中 PERV-A/C 高流行率的可能原因,包括近亲繁殖以及这些动物中具有更高数量和表达水平的复制型 PERV-C。基于这些数据,强烈建议在临床异种移植中仅使用 PERV-C 阴性的猪供体。