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Is it currently possible to evaluate the risk posed by PERV s for clinical xenotransplantation?
Author(s) -
Denner Joachim,
Scobie Linda,
Schuurman HenkJan
Publication year - 2018
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1111/xen.12403
Subject(s) - xenotransplantation , endogenous retrovirus , biology , computational biology , medicine , transplantation , genetics , gene , genome
The risk of transmission of porcine microorganisms is, in addition to the immunological rejection and the physiological incompatibilities, a major hurdle to the clinical use of pig cells, tissues, and organs for the treatment of organ failure in humans, to overcome the medical need caused by the increasing lack of human donors. Whereas most of the porcine microorganisms may be eliminated by early weaning, colostrum deviation, vaccination, antiviral drugs, animal isolation, cesarean delivery of newborns, and embryo transfer, porcine endogenous retroviruses (PERVs) cannot be eliminated this way because they are integrated in the genome of all pigs.1 Only a few years before evidence was published that PERV is able to infect human cells,2 two other retroviruses, simian immunodeficiency virus of chimpanzees (SIVcpz), and simian immunodeficiency virus from sooty mangabeys (SIVsm), now called human immunodeficiency viruses 1 and 2 (HIV1 and 2), invaded the human population causing the fatal acquired immunodeficiency syndrome (AIDS).3,4 Although HIV and PERVs are not very closely related, the fact that PERV is a retrovirus makes it so difficult to evaluate its risk.5 Also, although most retroviruses are immunosuppressive in the infected host, the absence of an animal model makes it difficult to show this for PERV.6 In recent years, several strategies have been exploited to evaluate the risk posed by PERV, such as (i) infection experiments in vitro, (ii) infection experiments in vivo in small laboratory animals and in nonhuman primates (NHPs) with and without immunosuppression, (iii) preclinical trials in NHPs transplanting pig cells and organs with and without immunosuppression and (iv) clinical trials mostly using encapsulated pig islet cells without immunosuppression. Despite these substantial efforts, these studies do not allow to make unequivocal conclusions whether PERVs pose a risk in the case of treatment of humans with porcine cells, tissues or solid organs, as will be discussed in the sections below. Unfortunately, there are no alternative approaches to test this in an experimental setting: essentially clinical trials are needed to answer this question.