Abstract
BackgroundXenotransplantation using pig cells, tissues and organs may help to overcome the shortage of human tissues and organs for the treatment of tissue and organ failure. Progress in the prevention of immunological rejection using genetically modified pigs and new, more effective, immunosuppression regimens will allow clinical application of xenotransplantation in near future. However, xenotransplantation may be associated with the transmission of potentially zoonotic porcine microorganisms. Until now the only xenotransplantation-associated transmission was the transmission of the porcine cytomegalovirus (PCMV) into non-human primates. PCMV caused a significant reduction of the survival time of the pig transplant.Main body of the abstractHere the available publications were analysed in order to establish the mechanism how PCMV shortened the survival time of xenotransplants. PCMV is a herpesvirus related to the human cytomegalovirus and the human herpesviruses 6 and 7. These three human herpesviruses can cause serious disease among immunocompromised human individuals, including transplant recipients. It was shown that PCMV predominantly contributes to the reduction of transplant survival in non-human primates by disruption of the coagulation system and by suppression and exhaustion of the immune system.ConclusionAlthough it is still unknown whether PCMV infects primate cells including human cells, indirect mechanism of the virus infection may cause reduction of the xenotransplant survival in future clinical trials and therefore PCMV has to be eliminated from donor pigs.
Highlights
ConclusionIt is still unknown whether porcine cytomegalovirus (PCMV) infects primate cells including human cells, indirect mechanism of the virus infection may cause reduction of the xenotransplant survival in future clinical trials and PCMV has to be eliminated from donor pigs
Risk evaluation of some porcine viruses Viruses affecting the health of the donor pigs will harm the transplant and have to be eliminated
Conclusion: it is still unknown whether porcine cytomegalovirus (PCMV) infects primate cells including human cells, indirect mechanism of the virus infection may cause reduction of the xenotransplant survival in future clinical trials and PCMV has to be eliminated from donor pigs
Summary
PCMV is the first virus with proven pathogenicity in xenotranplantation. In numerous preclinical trials transplanting pig organs into non-human primates, a significant reduction of the survival time was observed when the organs were PCMV-infected. The possible mechanisms of reduction of survival time are based on the disruption of the coagulation system and by suppression and exhaustion of the immune system. PCMV is resistant against antivirals which are effective against other herpesviruses and vaccines against PCMV do not exist, PCMV can eliminated by early weaning and isolation of the negative animals
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