Absence of transmission of potentially xenotic viruses in a prospective pig to primate islet xenotransplantation study

SUMMARY Xenotransplantation may be a solution to overcome the shortage of organs for the treatment of patients with organ failure, but it may be associated with the transmission of porcine microorganisms and the development of xenozoonoses. Whereas most microorganisms may be eliminated by pathogen-free breeding of the donor animals, porcine endogenous retroviruses (PERVs) cannot be eliminated, since these are integrated into the genomes of all pigs. Human-tropic PERV-A and -B are present in all pigs and are able to infect human cells. Infection of ecotropic PERV-C is limited to pig cells. PERVs may adapt to host cells by varying the number of LTR-binding transcription factor binding sites. Like all retroviruses, they may induce tumors and/or immunodeficiencies. To date, all experimental, preclinical, and clinical xenotransplantations using pig cells, tissues, and organs have not shown transmission of PERV. Highly sensitive and specific methods have been developed to analyze the PERV status of donor pigs and to monitor recipients for PERV infection. Strategies have been developed to prevent PERV transmission, including selection of PERV-C-negative, low-producer pigs, generation of an effective vaccine, selection of effective antiretrovirals, and generation of animals transgenic for a PERV-specific short hairpin RNA inhibiting PERV expression by RNA interference.

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“…There was no evidence for transmission of any of these pig viruses into the primate recipients (116).…”

Section: Pervsmentioning

confidence: 92%

Infection Barriers to Successful Xenotransplantation Focusing on Porcine Endogenous Retroviruses

2012

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“…In terms of overall success, despite several studies demonstrating the transmission of PERV in vivo (Argaw, ColonMoran & Wilson, 2004;Martina, Marcucci, Cherqui, Szabo, Drysdale et al, 2006;Popp, Mann, Milburn, Gibbs, McCullagh et al, 2007), no report has conclusively demonstrated productive infection (Denner, Specke, Karlas, Chodnevskaja, Meyer et al, 2008;HermidaPrieto, Domenech, Moscoso, Diaz, Ishii et al, 2007;Levy, Argaw, Wilson, Brooks, Sandstrom et al, 2007;Moscoso, Hermida-Prieto, Manez, Lopez-Pelaez, Centeno et al, 2005;Paradis, Langford, Long, Heneine, Sandstrom et al, 1999;Specke, Schuurman, Plesker, Coulibaly, Ozel et al, 2002). In terms of in vivo transmission from the AI pig herd no evidence of PERV infection was found in non-human primates following transplantation of islet cells (Garkavenko, Dieckhoff, Wynyard, Denner, Elliott et al, 2008) or in twelve human patients sampled from the New Zealand clinical trial (Wynyard, 2011).…”

Section: Perv Infectivity In Vivomentioning

confidence: 97%

Developing Xenostandards for Microbiological Safety: New Zealand Experience

Garkavenko¹,

Wynyard²,

Nathu³

et al. 2012

Xenotransplantation

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“…Breeding the animals under designated pathogen free (dpf) conditions will prevent at least the transmission of known zoonotic microorganisms such as circoviruses, herpesviruses and others [79]. Porcine cytomegalovirus (PCMV), porcine lymphotropic herpesvirus (PLHV), and porcine circovirus (PCV) are the main viruses screened for in the ongoing New Zealand clinical trial [80,81]. In contrast to these microorganisms transmission of porcine endogenous retroviruses (PERVs) cannot be prevented by dpf breeding since they are integrated as DNA copy in the genome of all pigs [101].…”

Section: Microbiological Safetymentioning

confidence: 99%

Xenotransplantation-Progress and Problems: A Review

Denner¹

2014

J Transplant Technol Res

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Xenotransplantation using pig cells, tissues or organs is considered to be a solution to the shortage of human allotransplants. Pigs have been selected as optimal donor for several reasons, among them physiological and economical. Before xenotransplantation will be applied broadly in the clinic three hurdles need to be overcome: (i) rejection due to immune reactions and coagulation dysfunction, (ii) physiological incompatibility and (iii) microbiological risk. Although some clinical trials have been performed in the past and some are ongoing, most experience is gained from pig-to-non human primate experiments. To overcome immune rejection, numerous multitransgenic and knock-down animals were produced or are in preparation. The physiological compatibility is still badly studied, mainly due to the short survival time of the recipient animals. Last not least, xenotransplantation may be associated with the risk of transmission of porcine microorganisms. Most of them can be eliminated by designated pathogen free breeding of the animals; however, porcine endogenous retroviruses (PERVs) represent a special risk. PERVs are integrated as proviruses in the genome of all pigs, they can be released as viral particles and infect human cells. An extensive screening program and selection of donor animals with a low expression of PERV accompanied by the development of different strategies to prevent PERV transmission is therefore requested. Finally, a broad discussion within the scientific community and the society concerning ethical aspects of xenotransplantation had been taken place.

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Absence of transmission of potentially xenotic viruses in a prospective pig to primate islet xenotransplantation study

Cited by 76 publications

References 52 publications

Infection Barriers to Successful Xenotransplantation Focusing on Porcine Endogenous Retroviruses

Infection Barriers to Successful Xenotransplantation Focusing on Porcine Endogenous Retroviruses

Developing Xenostandards for Microbiological Safety: New Zealand Experience

Xenotransplantation-Progress and Problems: A Review

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