Xenotransplantation and Porcine Endogenous Retroviruses

Dear Editor, The Indian Journal of Kidney Diseases published an excellent review on xenotransplantation by Sejpal and Priyamvada.[1] The authors described all important aspects of this new technology which is under development in order to alleviate the shortage of human donor organs. Unfortunately, the authors made a small mistake, and were wrongly referring to a publication of mine. Discussing the bioethical issues, they correctly mentioned the putative risk posed by porcine endogenous retroviruses (PERVs), which are integrated in the genome of all pigs and which therefore cannot be eliminated as all other viruses can. However, they claim, that “if transferred to humans, PERVs might be capable of reaching epidemic proportions as humans lack immunity against the viruses,” citing a reference of mine which does not contain evidence for this. In the cited paper, I demonstrated that PERVs are active in living pigs, able to increase the number of integrated proviruses and able to recombine.[2] Although there was no transmission of PERV to humans and non-human primates in first clinical and preclinical trials,[3] it is very likely that humans can establish immunity against PERVs. This is based on the fact that infections with exogenous retroviruses such as human immunodeficiency viruses (HIVs) and human T-lymphotropic viruses (HTLVs) are always associated with a strong immune response in infected humans and this immune response is used for diagnostic purposes.[4] As a matter of fact, PERVs have, like all retroviruses, immunosuppressive properties,[5] however, this does not prevent an antiviral immune response as seen in the case of HIVs and HTLVs. Furthermore, strong binding and neutralizing antibodies have been induced in animal species after immunization with the transmembrane and surface envelope proteins of PERV. Therefore, it seems possible to vaccinate the xenotransplant recipient against PERV in order to prevent a transmission of the virus. The fact that different animal species, such as goats, guinea pigs, rabbits, rats, and mice produced neutralizing antibodies after immunization with the envelope proteins of PERV suggests that such a response may be very likely achieved also in humans.[6] In addition, the authors should have mentioned that other porcine viruses such as the porcine cytomegalovirus, which is actually a porcine roseolovirus (PCMV/PRV) and others, also pose a risk for the recipient. PCMV/PRV was shown to reduce drastically the survival time of non-human primates transplanted with PCMV/PRV-positive heart and kidney xenotransplants. Meanwhile, we know that this virus was transmitted to the first patient receiving a pig heart in Baltimore and that it contributed to the death of the patient.[7] Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.