title: Pig islet xenotransplantation: activation of porcine endogenous retrovirus in the immediate post-transplantation period.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: The Rudbeck Laboratory, Division of Clinical Immunology, Uppsala University, Uppsala, Sweden. peter.schmidt@klinimm.uu.se
authors.forename: Peter
authors.initials: P
authors.lastname: Schmidt
authors.forename: Anna
authors.initials: A
authors.lastname: Forsman
authors.forename: Göran
authors.initials: G
authors.lastname: Andersson
authors.forename: Jonas
authors.initials: J
authors.lastname: Blomberg
authors.forename: Olle
authors.initials: O
authors.lastname: Korsgren
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D020077:Endogenous Retroviruses / Q000502:physiology*; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects*; D011184:Postoperative Period; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D012192:Retroviridae Infections / Q000821:virology*; D013552:Swine / Q000821:virology*; D013997:Time Factors; D014183:Transplantation, Heterologous; D014775:Virus Activation
chemical_list: D012333:RNA, Messenger