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2009-02-16Zeitschriftenartikel DOI: 10.1111/j.1399-3089.2009.00508.x
No in vivo infection of triple immunosuppressed non-human primates after inoculation with high titers of porcine endogenous retroviruses
dc.contributor.authorSpecke, Volker
dc.contributor.authorPlesker, Roland
dc.contributor.authorWood, James
dc.contributor.authorCoulibaly, Cheick
dc.contributor.authorSuling, Kristen
dc.contributor.authorPatience, Clive
dc.contributor.authorKurth, Reinhard
dc.contributor.authorSchuurman, Henk-Jan
dc.contributor.authorDenner, Joachim
dc.date.accessioned2018-05-07T13:56:02Z
dc.date.available2018-05-07T13:56:02Z
dc.date.created2010-06-09
dc.date.issued2009-02-16none
dc.identifier.otherhttp://edoc.rki.de/oa/articles/reUctUWxBkAIU/PDF/29EHzryK83PYs.pdf
dc.identifier.urihttp://edoc.rki.de/176904/658
dc.description.abstractBackground: Porcine endogenous retroviruses (PERVs) released from pig tissue can infect selected human cells in vitro and therefore represent a safety risk for xenotransplantation using pig cells, tissues, or organs. Although PERVs infect cells of numerous species in vitro, attempts to establish reliable animal models failed until now. Absence of PERV transmission has been shown in first experimental and clinical xenotransplantations; however, these trials suffered from the absence of long-term exposure (transplant survival) and profound immunosuppression. Methods: We conducted infectivity studies in rhesus monkeys, pig-tailed monkeys, and baboons under chronic immunosuppression with cyclosporine A, methylprednisolone, and the rapamycin derivative. These species were selected because they are close to the human species and PERVs can be transmitted in vitro to cells of these species. In addition, the animals received twice, a C1 esterase inhibitor to block complement activation before inoculation of PERV. In order to overcome the complications of microchimerism, animals were inoculated with high titers of cell-free PERV. In addition, to enable transmission via cell–cell contact, some animals also received virus-producing cells. For inoculation the primate cell-adapted strain PERV/5° was used which is characterized by a high infectious titer. Produced on human cells, this virus does not express alpha 1,3 Gal epitopes, does not contain porcine antigens on the viral surface and is therefore less immunogenic in non-human primates compared with pig cell-derived virus. Finally, we present evidence that PERV/5° productively infects cells from baboons and rhesus monkeys. Results: In a follow-up period of 11 months, no antibody production against PERV and no integration of proviral DNA in blood cells was observed. Furthermore, no PERV sequences were detected in the DNA of different organs taken after necropsy. Conclusion: These results indicate that in a primate model, in the presence of chronic immunosuppression, neither the inoculation of cell-free nor cell-associated PERV using a virus already adapted to primate cells results in an infection; this is despite the fact that peripheral blood mononuclear cells of the same animals are infectible in vitro.eng
dc.language.isoeng
dc.publisherRobert Koch-Institut
dc.subjectAnimalseng
dc.subjectDNAeng
dc.subjectFemaleeng
dc.subjectMaleeng
dc.subjectViral/bloodeng
dc.subjectTransplantationeng
dc.subjectHeterologouseng
dc.subjectCyclosporine/therapeutic useeng
dc.subjectDrug Therapyeng
dc.subjectCombinationeng
dc.subjectEndogenous Retroviruses/geneticseng
dc.subjectEndogenous Retroviruses/pathogenicityeng
dc.subjectImmunosuppressive Agents/therapeutic useeng
dc.subjectMacaca mulatta/immunologyeng
dc.subjectMacaca nemestrina/immunologyeng
dc.subjectMethylprednisolone/therapeutic useeng
dc.subjectPapio/immunologyeng
dc.subjectPrimate Diseases/immunologyeng
dc.subjectPrimate Diseases/prevention & controleng
dc.subjectPrimate Diseases/virologyeng
dc.subjectRetroviridae Infections/immunologyeng
dc.subjectRetroviridae Infections/prevention & controleng
dc.subjectRetroviridae Infections/veterinaryeng
dc.subjectSirolimus/therapeutic useeng
dc.subjectSwine/virologyeng
dc.subject.ddc610 Medizin
dc.titleNo in vivo infection of triple immunosuppressed non-human primates after inoculation with high titers of porcine endogenous retroviruses
dc.typeperiodicalPart
dc.identifier.urnurn:nbn:de:0257-1009112
dc.identifier.doi10.1111/j.1399-3089.2009.00508.x
dc.identifier.doihttp://dx.doi.org/10.25646/583
local.edoc.container-titleXenotransplantation
local.edoc.container-textSpecke, V., Plesker, R., Wood, J., Coulibaly, C., Suling, K., Patience, C., Kurth, R., Schuurman, H.-J., Denner, J. No in vivo infection of triple immunosuppressed non-human primates after inoculation with high titers of porcine endogenous retroviruses (2009) Xenotransplantation, 16 (1), pp. 34-44.
local.edoc.fp-subtypeArtikel
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-urlhttp://www3.interscience.wiley.com
local.edoc.container-publisher-nameWiley
local.edoc.container-volume16
local.edoc.container-issue1
local.edoc.container-year2009

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