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. 2008 Dec;82(24):12441-8.
doi: 10.1128/JVI.01278-08. Epub 2008 Oct 1.

Absence of replication of porcine endogenous retrovirus and porcine lymphotropic herpesvirus type 1 with prolonged pig cell microchimerism after pig-to-baboon xenotransplantation

Nicolas C Issa  1 , Robert A Wilkinson, Adam Griesemer, David K C Cooper, Kazuhiko Yamada, David H Sachs, Jay A Fishman
Affiliations

Absence of replication of porcine endogenous retrovirus and porcine lymphotropic herpesvirus type 1 with prolonged pig cell microchimerism after pig-to-baboon xenotransplantation

Nicolas C Issa et al. J Virol. 2008 Dec.

Abstract

Porcine endogenous retrovirus (PERV), porcine cytomegalovirus (PCMV), and porcine lymphotropic herpesvirus (PLHV) are common porcine viruses that may be activated with immunosuppression for xenotransplantation. Studies of viral replication or transmission are possible due to prolonged survival of xenografts in baboon recipients from human decay-accelerating factor transgenic or alpha-1,3-galactosyltransferase gene knockout miniature swine. Ten baboons underwent xenotransplantation with transgenic pig organs. Graft survival was 32 to 179 days. Recipient serial samples of peripheral blood mononuclear cells (PBMC) and plasma were analyzed for PCMV, PERV, and PLHV-1 nucleic acids and viral replication using quantitative PCR assays. The PBMC contained PERV proviral DNA in 10 animals, PLHV-1 DNA in 6, and PCMV in 2. PERV RNA was not detected in any PBMC or serum samples. Plasma PLHV-1 DNA was detected in one animal. Pig cell microchimerism (pig major histocompatibility complex class I and pig mitochondrial cytochrome c oxidase subunit II sequences) was present in all recipients with detectable PERV or PLHV-1 (85.5%). Productive infection of PERV or PLHV-1 could not be demonstrated. The PLHV-1 viral load did not increase in serum over time, despite prolonged graft survival and pig cell microchimerism. There was no association of viral loads with the nature of exogenous immune suppression. In conclusion, PERV provirus and PLHV-1 DNA were detected in baboons following porcine xenotransplantation. Viral detection appeared to be due to persistent pig cell microchimerism. There was no evidence of productive infection in recipient baboons for up to 6 months of xenograft function.

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Figures

FIG. 1.
FIG. 1.
Viral loads of PLHV-1, PERV pol, MHC-I, mtCOII, and BCMV in baboon B113. POD, postoperative day.
FIG. 2.
FIG. 2.
Viral loads of PLHV-1, PERV pol, MHC-I, mtCOII, and BCMV in baboon B114. POD, postoperative day.
FIG. 3.
FIG. 3.
MMF levels, tacrolimus (FK) levels, and PERV pol viral loads in baboons. (A) FK (FKB113) levels and PERV pol (PERVB113) viral loads (number of copies/200 ng of DNA) (secondary y axis) in baboon B113. (B) PERV pol (PERVB113) viral loads (number of copies/200 ng of DNA) (primary y axis) and MMF (MMFB113) levels in baboon B113. (C) FK (FKB114) levels and PERV pol (PERVB114) viral loads in baboon B114. (D) PERV pol (PERVB114) viral loads (number of copies/200 ng of DNA) (primary y axis) and MMF (MMFB114) levels in baboon B114. POD, postoperative day.
FIG. 3.
FIG. 3.
MMF levels, tacrolimus (FK) levels, and PERV pol viral loads in baboons. (A) FK (FKB113) levels and PERV pol (PERVB113) viral loads (number of copies/200 ng of DNA) (secondary y axis) in baboon B113. (B) PERV pol (PERVB113) viral loads (number of copies/200 ng of DNA) (primary y axis) and MMF (MMFB113) levels in baboon B113. (C) FK (FKB114) levels and PERV pol (PERVB114) viral loads in baboon B114. (D) PERV pol (PERVB114) viral loads (number of copies/200 ng of DNA) (primary y axis) and MMF (MMFB114) levels in baboon B114. POD, postoperative day.
FIG. 4.
FIG. 4.
PERV pol and BCMV viral loads and tacrolimus (FK506) levels in baboons. (A) PERV pol and BCMV viral loads (number of copies/200 ng of DNA) (primary y axis) and FK506 (secondary y axis) in baboon B109; (B) PERV pol and BCMV viral loads (number of copies/200 ng of DNA) (primary y axis) and FK506 (secondary y axis) in baboon B110. POD, postoperative days.
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References

    1. Argaw, T., W. Colon-Moran, and C. A. Wilson. 2004. Limited infection without evidence of replication by porcine endogenous retrovirus in guinea pigs. J. Gen. Virol. 8515-19. - PubMed
    1. Blusch, J. H., C. Patience, Y. Takeuchi, C. Templin, C. Roos, K. Von Der Helm, G. Steinhoff, and U. Martin. 2000. Infection of nonhuman primate cells by pig endogenous retrovirus. J. Virol. 747687-7690. - PMC - PubMed
    1. Chmielewicz, B., M. Goltz, T. Franz, C. Bauer, S. Brema, H. Ellerbrok, S. Beckmann, H. J. Rziha, K. H. Lahrmann, C. Romero, and B. Ehlers. 2003. A novel porcine gammaherpesvirus. Virology 308317-329. - PubMed
    1. Cho, P. S., N. J. Mueller, A. M. Cameron, R. A. Cina, R. C. Coburn, S. Hettiaratchy, E. Melendy, D. M. Neville, Jr., C. Patience, J. A. Fishman, D. H. Sachs, and C. A. Huang. 2004. Risk factors for the development of post-transplant lymphoproliferative disorder in a large animal model. Am. J. Transplant. 41274-1282. - PubMed
    1. Cunningham, D. A., G. J. Dos Santos Cruz, X. M. Fernandez-Suarez, A. J. Whittam, C. Herring, L. Copeman, A. Richards, and G. A. Langford. 2004. Activation of primary porcine endothelial cells induces release of porcine endogenous retroviruses. Transplantation 771071-1079. - PubMed

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