title: Porcine cytomegalovirus infection is associated with early rejection of kidney grafts in a pig to baboon xenotransplantation model.
abstract: BACKGROUND
  Recent survivals of our pig-to-baboon kidney xenotransplants have been markedly shorter than the graft survivals we previously reported. The discovery of high levels of porcine cytomegalovirus (pCMV) in one of the rejected xenografts led us to evaluate whether this reduction in graft survival might be because of the inadvertent introduction of pCMV into our α1,3-galactosyltransferase gene knockout swine herd.
  
  
  METHODS
  Archived frozen sections of xeno-kidney grafts over the past 10 years were analyzed for the presence of pCMV, using real-time polymerase chain reaction. Three prospective pig-to-baboon renal transplants using kidneys from swine delivered by cesarean section (C-section) and raised in isolation were likewise analyzed.
  
  
  RESULTS
  Kidney grafts, from which 8 of the 18 archived samples were derived were found to be pCMV-negative, showed a mean graft survival of 48.3 days and were from transplants performed before 2008. None showed signs of disseminated intravascular coagulopathy and were lost because of proteinuria or infectious complications. In contrast, 10 of the archived samples were pCMV positive, were from kidney transplants with a mean graft survival of 14.1 days, had been performed after 2008, and demonstrated early vascular changes and decreased platelet counts. Three prospective xenografts from swine delivered by C-section were pCMV negative and survived an average of 53.0 days.
  
  
  CONCLUSIONS
  Decreased survivals of α1,3-galactosyltransferase gene knockout renal xenografts in this laboratory correlate temporally with latent pCMV in the donor animals and pCMV in the rejected xeno-kidneys. Transmission of pCMV to swine offspring may be avoided by C-section delivery and scrupulous isolation of donor animals.
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Cambridge, MA. 1 Address correspondence to: Kazuhiko Yamada, M.D., Ph.D., Organ Transplantation Tolerance and Xenotransplantation Laboratory, Transplantation Biology Research Center, Massachusetts General Hospital, MGH-East, Bldg. 149-9019, 13th Street, Boston, MA, 02129.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamada
authors.forename: Masayuki
authors.initials: M
authors.lastname: Tasaki
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Sekijima
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wilkinson
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Villani
authors.forename: Shannon G
authors.initials: SG
authors.lastname: Moran
authors.forename: Taylor A
authors.initials: TA
authors.lastname: Cormack
authors.forename: Isabel M
authors.initials: IM
authors.lastname: Hanekamp
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Hawley
authors.forename: J Scott
authors.initials: JS
authors.lastname: Arn
authors.forename: Jay A
authors.initials: JA
authors.lastname: Fishman
authors.forename: Akira
authors.initials: A
authors.lastname: Shimizu
authors.forename: David H
authors.initials: DH
authors.lastname: Sachs
mesh_terms: D000818:Animals; D003586:Cytomegalovirus Infections / Q000150:complications*; D005260:Female; D005700:Galactosyltransferases / Q000502:physiology; D006084:Graft Rejection / Q000209:etiology*; D006085:Graft Survival; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D048529:Papio hamadryas; D013552:Swine; D023001:Transplantation Tolerance; D014183:Transplantation, Heterologous
chemical_list: D018799:Intercellular Adhesion Molecule-1; D005700:Galactosyltransferases; C047006:N-acetyllactosaminide alpha-1,3-galactosyltransferase