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在猪胰岛细胞异种移植受者中未发现感染猪内源性逆转录病毒的证据。

No evidence of infection with porcine endogenous retrovirus in recipients of porcine islet-cell xenografts.

作者信息

Heneine W, Tibell A, Switzer W M, Sandstrom P, Rosales G V, Mathews A, Korsgren O, Chapman L E, Folks T M, Groth C G

机构信息

HIV and Retrovirology Branch, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.

出版信息

Lancet. 1998 Aug 29;352(9129):695-9. doi: 10.1016/S0140-6736(98)07145-1.

DOI:10.1016/S0140-6736(98)07145-1
PMID:9728986
Abstract

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.

摘要

背景

研究猪异种移植物是否会导致受体感染猪内源性逆转录病毒(PERV)对于评估猪到人的异种移植安全性至关重要。PERV存在于猪的种系中,所有接受猪组织或器官的受体都将接触到该病毒。

方法

我们研究了1990年至1993年间接受猪胎儿胰岛移植的10名糖尿病患者,通过聚合酶链反应(PCR)血清学、PCR和逆转录酶检测寻找PERV感染的证据。通过猪C肽排泄和血清中猪线粒体DNA(mtDNA)的检测,证实了5名患者的异种移植物存活时间延长(长达一年)。

研究结果

尽管有证据表明患者长期接触猪细胞,且同时接受了免疫抑制治疗,但我们在任何患者中均未检测到PERV感染的标志物。对异种移植后4至7年采集的外周血淋巴细胞中的两个PERV序列进行筛查,结果为阴性。在早期(第3天至第180天)和晚期(4至7年)时间点的血清中均未检测到PERV表达的标志物,包括病毒RNA和逆转录酶。抗体的蛋白质印迹分析结果始终为阴性。

解读

这些结果表明这些患者未感染PERV。此外,本研究还为接受猪异种移植物患者的移植后监测确立了最低标准。

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