Lack of Cross-Species Transmission of Porcine Endogenous Retrovirus in Pig-to-Baboon Xenotransplantation with Sustained Depletion of Anti-??Gal Antibodies

Abstract

Sustained depletion of anti-alphaGal antibodies does not augment the risk of PERV infection in pig-to-baboon organ transplantation.

Absence of Replication of Porcine Endogenous Retrovirus and Porcine Lymphotropic Herpesvirus Type 1 with Prolonged Pig Cell Microchimerism after Pig-to-Baboon Xenotransplantation

“…This likely reflects similarities in the numbers of active PERV loci in the hDAF and GalT-KO swine (J. Fishman and L. Scobie, preliminary data). Previous studies using the depletion of anti-␣-Gal antibodies in 27 baboon recipients of hDAF or human membrane cofactor protein/hDAF transgenic pig organs, which were followed for over 2 months, also failed to show evidence of PERV replication (27). These data are consistent with the failure to demonstrate PERV replication in xenograft recipients (27,48).…”

“…Previous studies using the depletion of anti-␣-Gal antibodies in 27 baboon recipients of hDAF or human membrane cofactor protein/hDAF transgenic pig organs, which were followed for over 2 months, also failed to show evidence of PERV replication (27). These data are consistent with the failure to demonstrate PERV replication in xenograft recipients (27,48). Apparent PERV infection of human cells in a pig-to-SCID mouse model following islet cell transplantation was shown to be due to the pseudotyping of PERV by endogenous murine retroviruses rather than PERV infection of human cells (52).…”

“…No productive infections due to PERV in vivo have been described for humans exposed to porcine tissues or for nonhuman primates following xenotransplantation (6-9, 16, 34, 35, 38, 41). The transmission and detection of PERV proviral DNA attributed to pig cell microchimerism have been described for guinea pigs (1), mice (20), and baboons (27,48) but without evidence of viral replication in host cells. Reported PERV infection of human cells in mice was shown to be due to the pseudotyping of PERV by endogenous murine retroviruses rather than direct viral infection (52).…”

Developing Xenostandards for Microbiological Safety: New Zealand Experience

“…Subsequent analysis revealed that this was not a true infection but rather evidence of pseudotyping involving the collaboration of mouse (endogenous xenotropi c M LV ) and PE RV r etro v ira l e lem ents (Martina, Kurian, Cherqui, Evanoff, Wilson et al, 2005). 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).…”

Methods and Tools for Detection and Evaluation of the Risks of Porcine Endogenous Retrovirus in Porcine to Human Xenotransplantation

“…These findings were confirmed and extended in a recent study that showed that the ortholog for the PERV-A receptor in rhesus macaque and baboon is non-functional. Similarly, in vivo studies have not found evidence for PERV transmission in NHP transplanted with porcine xenotransplantation products, even when using potent immunosuppression treatments (Moscoso, Hermida-Prieto et al 2005;Specke, Plesker et al 2009). Together, these findings reinforce the conclusion that NHP are not a permissive model for studying the risks of PERV exposure to porcine xenotransplantation recipients.…”