BACKGROUND: The study of whether porcine xenografts can lead to porcine endogenous retrovirus (PERV) infection of recipients is critical for evaluating the safety of pig-to-man xenotransplantation. PERV is carried in the pig germline, and all recipients of porcine tissues or organs will be exposed to the virus. METHODS: We studied 10 diabetic patients who had received porcine fetal islets between 1990 and 1993, looking for evidence of PERV infection by using PCR serology, PCR, and reverse transcriptase assays. Prolonged xenograft survival (up to a year) was confirmed in five patients by porcine C-peptide excretion and detection of pig mitochondrial DNA (mtDNA) in serum. FINDINGS: Despite the evidence for extended exposure to pig cells and despite concomitant immunosuppressive therapy, we were unable to detect markers of PERV infection in any patient. Screening for two PERV sequences in peripheral blood lymphocytes collected 4-7 years after the xenotransplantation was negative. Markers of PERV expression, including viral RNA and reverse transcriptase, were undetectable in sera from both early (day 3 to day 180) and late (4-7 years) time points. Western blot analysis for antibodies was consistently negative. INTERPRETATION: These results suggested the absence of PERV infection in these patients. Also this study establishes a minimum standard for post-transplant surveillance of patients given porcine xenografts.
BACKGROUND: The study of whether porcine xenografts can lead to porcine endogenous retrovirus (PERV) infection of recipients is critical for evaluating the safety of pig-to-man xenotransplantation. PERV is carried in the pig germline, and all recipients of porcine tissues or organs will be exposed to the virus. METHODS: We studied 10 diabeticpatients who had received porcine fetal islets between 1990 and 1993, looking for evidence of PERVinfection by using PCR serology, PCR, and reverse transcriptase assays. Prolonged xenograft survival (up to a year) was confirmed in five patients by porcine C-peptide excretion and detection of pig mitochondrial DNA (mtDNA) in serum. FINDINGS: Despite the evidence for extended exposure to pig cells and despite concomitant immunosuppressive therapy, we were unable to detect markers of PERVinfection in any patient. Screening for two PERV sequences in peripheral blood lymphocytes collected 4-7 years after the xenotransplantation was negative. Markers of PERV expression, including viral RNA and reverse transcriptase, were undetectable in sera from both early (day 3 to day 180) and late (4-7 years) time points. Western blot analysis for antibodies was consistently negative. INTERPRETATION: These results suggested the absence of PERVinfection in these patients. Also this study establishes a minimum standard for post-transplant surveillance of patients given porcine xenografts.
Authors: Stephen T Bartlett; James F Markmann; Paul Johnson; Olle Korsgren; Bernhard J Hering; David Scharp; Thomas W H Kay; Jonathan Bromberg; Jon S Odorico; Gordon C Weir; Nancy Bridges; Raja Kandaswamy; Peter Stock; Peter Friend; Mitsukazu Gotoh; David K C Cooper; Chung-Gyu Park; Phillip OʼConnell; Cherie Stabler; Shinichi Matsumoto; Barbara Ludwig; Pratik Choudhary; Boris Kovatchev; Michael R Rickels; Megan Sykes; Kathryn Wood; Kristy Kraemer; Albert Hwa; Edward Stanley; Camillo Ricordi; Mark Zimmerman; Julia Greenstein; Eduard Montanya; Timo Otonkoski Journal: Transplantation Date: 2016-02 Impact factor: 4.939