Pig islet xenotransplantation: activation of porcine endogenous retrovirus in the immediate post-transplantation period
- 1 November 2005
- journal article
- Published by Wiley in Xenotransplantation
- Vol. 12 (6), 450-456
- https://doi.org/10.1111/j.1399-3089.2005.00244.x
Abstract
Porcine endogenous retroviruses (PERV) are considered as the main infectious barrier in islet xenotransplantation. PERV has been shown to infect, but not to cause symptomatic disease in mice after islet transplantation. In vivo activation of PERV have so far not been examined. Expression of PERV was examined in adult and fetal porcine islets with or without the presence of known retroviral inducers or after transplantation to rats. Isolated adult and fetal porcine islets were cultured under normal conditions or in the presence of dexamethasone or 5-azacytidine and 5-iodo-2-deoxyuridine. PERV mRNA content was analyzed by real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and culture supernatants were analyzed for the presence of retroviral RT. Also, fetal islets were transplanted under the kidney capsule of immunocompetent or nude athymic rats. Expression of PERV mRNA in the grafts was evaluated by real-time quantitative RT-PCR. Infiltration of immunocompetent cells were evaluated by immunohistochemistry. Both fetal and adult islets in culture produced small or even undetectable amounts of PERV mRNA and retroviral RT. PERV expression was not enhanced by retroviral inducers. In contrast, activation of PERV expression was observed the first day after transplantation of fetal islet-like cell clusters in both athymic and normal rats. PERV expression peaked after 1 to 3 days and was then rapidly returned to background levels. PERV expression neither correlated with the innate immune response seen in athymic rats nor with the specific process of rejection in normal rats. Both fetal and adult islets produce low amounts of PERV mRNA in culture. After transplantation PERV expression is induced, seemingly independent of both the unspecific inflammatory response and the specific T-cell-mediated rejection process. It is speculated that PERV expression is correlated with the level of hypoxia in the islet xenograft.Keywords
This publication has 29 references indexed in Scilit:
- ERV3 and Related Sequences in Humans: Structure and RNA ExpressionJournal of Virology, 2005
- Xenotransplantation: Infectious Risk RevisitedAmerican Journal of Transplantation, 2004
- Transcriptional Regulation of Porcine Endogenous Retroviruses Released from Porcine and Infected Human Cells by Heterotrimeric Protein Complex NF-Y and Impact of Immunosuppressive DrugsJournal of Virology, 2002
- Porcine Endogenous Retrovirus Transmission Characteristics of an Inbred Herd of Miniature SwineJournal of Virology, 2002
- Identification of Novel Porcine Endogenous Betaretrovirus Sequences in Miniature SwineJournal of Virology, 2001
- Susceptibility of the Porcine Endogenous Retrovirus to Reverse Transcriptase and Protease InhibitorsJournal of Virology, 2001
- Sensitization of cells and retroviruses to human serum by (αl-3) galactosyltransferaseNature, 1996
- THE MAIN INFILTRATING CELL IN XENOGRAFT REJECTION IS A CD4+ MACROPHAGE AND NOT A T LYMPHOCYTETransplantation, 1995
- TRANSPLANTATION OF FETAL PORCINE PANCREAS TO DIABETIC OR NORMOGLYCEMIC NUDE MICETransplantation, 1995
- Hyperglycemia-induced B cell toxicity. The fate of pancreatic islets transplanted into diabetic mice is dependent on their genetic background.JCI Insight, 1990