A new arenavirus in a cluster of fatal transplant-associated diseases
A new arenavirus in a cluster of fatal transplant-associated diseases
复制标题
DOI：
10.1056/nejmoa073785
复制
发表时间：
2008-03-06
影响因子：
158.5
通讯作者：
Lipkin, W. Ian
中科院分区：
文献类型：
--
作者：
Palacios, Gustavo;Druce, Julian;Lipkin, W. Ian
背景资料：三名患者在同一天接受了来自同一供体的器官移植，在移植后4至6周死于发热性疾病。文化，聚合酶链反应（PCR）和血清学检测，和寡核苷酸微阵列分析广泛的传染agents.Methods：我们评估了RNA从肝和肾移植受者。无偏高通量测序用于鉴定通过其他方法未发现的微生物序列。一个新的候选病原体的序列的特异性被证实通过培养和PCR，免疫组化和血清学analysis.Results的装置：高通量测序产生103,632序列，其中14个代表旧世界沙粒病毒。进一步的序列分析表明，这种新的沙粒病毒与淋巴细胞性脉络丛脑膜炎病毒有关。基于独特序列的特异性PCR检测证实了受体肾脏、肝脏、血液和脑脊液中存在病毒。免疫组织化学分析显示，在接受者的肝脏和肾脏移植沙粒病毒抗原。献血员血清中抗病毒抗体检测结果为IgM和IgG。血清转化是明显的血清标本从一个收件人在两个时间points.Conclusions：无偏高通量测序是一个强大的工具，发现病原体。在疾病爆发期间使用这种方法有助于鉴定通过实体器官移植传播的新型沙粒病毒。
Background: Three patients who received visceral-organ transplants from a single donor on the same day died of a febrile illness 4 to 6 weeks after transplantation. Culture, polymerase-chain-reaction (PCR) and serologic assays, and oligonucleotide microarray analysis for a wide range of infectious agents were not informative.Methods: We evaluated RNA obtained from the liver and kidney transplant recipients. Unbiased high-throughput sequencing was used to identify microbial sequences not found by means of other methods. The specificity of sequences for a new candidate pathogen was confirmed by means of culture and by means of PCR, immunohistochemical, and serologic analyses.Results: High-throughput sequencing yielded 103,632 sequences, of which 14 represented an Old World arenavirus. Additional sequence analysis showed that this new arenavirus was related to lymphocytic choriomeningitis viruses. Specific PCR assays based on a unique sequence confirmed the presence of the virus in the kidneys, liver, blood, and cerebrospinal fluid of the recipients. Immunohistochemical analysis revealed arenavirus antigen in the liver and kidney transplants in the recipients. IgM and IgG antiviral antibodies were detected in the serum of the donor. Seroconversion was evident in serum specimens obtained from one recipient at two time points.Conclusions: Unbiased high-throughput sequencing is a powerful tool for the discovery of pathogens. The use of this method during an outbreak of disease facilitated the identification of a new arenavirus transmitted through solid-organ transplantation.