Porcine Lymphotropic Herpesviruses (PLHVs) and Xenotranplantation

Abstract

Porcine lymphotropic herpesviruses -1, -2 and -3 (PLHV-1, PLHV-2 and PLHV-3) are gammaherpesviruses which are widespread in pigs. They are closely related to the Epstein–Barr virus (EBV) and Kaposi sarcoma herpesvirus, both of which cause severe diseases in humans. PLHVs are also related to bovine and ovine gammaherpesviruses, which are apathogenic in the natural host, but cause severe diseases after transmission into other species. Until now, no association between PLHVs and any pig diseases had been described. However, PLHV-1 causes a post-transplantation lymphoproliferative disorder (PTLD) after experimental transplantations in minipigs. This disorder is similar to human PTLD, a serious complication of solid human organ transplantation linked to EBV. Xenotransplantation using pig cells, tissues and organs is under development in order to alleviate the shortage of human transplants. Meanwhile, remarkable survival times of pig xenotransplants in non-human primates have been achieved. In these preclinical trials, another pig herpesvirus, the porcine cytomegalovirus (PCMV), a roseolovirus, was shown to significantly reduce the survival time of pig xenotransplants in baboons and other non-human primates. Although PLHV-1 was found in genetically modified donor pigs used in preclinical xenotransplantation, it was, in contrast to PCMV, not transmitted to the recipient. Nevertheless, it seems important to use PLHV-free donor pigs in order to achieve safe xenotransplantation.