Detecting contagious Epstein-Barr viruses in the saliva of transplant recipients

检测移植受者唾液中的传染性 Epstein-Barr 病毒

• 批准号: 400669527
• 负责人: Dr. Susanne E. K. Delecluse
• 金额: --
• 依托单位: Abteilung Pathogenese infektionsbedingter Tumoren
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/400669527?language=en
• 关键词: Detecting; contagious; Epstein; Barr; viruses

The Epstein-Barr virus (EBV) infects the large majority of the human population, usually without clinical consequences. If infection is delayed until adolescence, an infectious mononucleosis (IM) syndrome can develop. EBV is responsible for approximately 2% of all tumours worldwide, including lymphomas and carcinomas. Immunodeficiency, e.g. in transplant carriers, has been identified as a major risk factor for the development of EBV-positive posttransplant lymphoproliferative disorders known as PTLD. PTLDs represent 10% of all post-transplant malignancies and are associated with an EBV infection in about 60% of all cases. EBV primary infection after transplantation remains a strong risk factor for PTLD development. EBV is orally transmitted via saliva and is believed to firstly infect epithelial cells in which lytic replication takes place. Newly assembled viral particles are shed into saliva or infect nearby B cells in which EBV establishes a lifelong latent infection. The expression of viral latent and lytic proteins is responsible for the transformation of healthy B cells into malignant lymphoproliferations. EBV reactivation in EBV-positive transplant recipients is a frequent observation. Lytic replication and the expression of latent viral proteins in B cells, as well as the detection of EBV DNA, in the saliva are characteristics of IM and EBV reactivation. However, it is unknown whether transplant recipients actually shed infectious viral particles, defective virions or only fragmented EBV DNA. Consequently, it is not known whether these patients are contagious, representing a risk for EBV-negative individuals that are at increased risk of developing PTLD. The study aims to analyse saliva of transplant recipients with EBV reactivation to determine the origin of EBV DNA it contains. To this end, we propose to perform quantitative PCR studies, combined with virus binding and transformation assays to quantify the infectious virus load in saliva. This test could easily translated into clinical practice and help identifying high-risk patients. In future interventional studies patients shedding contagious EBV will be isolated or receive a preemptive therapy to determine the reduction rate of PTLD.

EB病毒（EBV）感染绝大多数人群，通常没有临床后果。如果感染延迟到青春期，可发展为传染性单核细胞增多症（IM）综合征。EBV是全球所有肿瘤的约2%，包括淋巴瘤和癌。免疫缺陷，例如在移植携带者中，已被确定为发生EBV阳性移植后淋巴增生性疾病（称为PTLD）的主要风险因素。PTLD占所有移植后恶性肿瘤的10%，约60%的病例与EBV感染相关。移植后EBV原发性感染仍然是PTLD发展的一个强有力的危险因素。EBV通过唾液经口传播，并且被认为首先感染上皮细胞，在上皮细胞中发生裂解性复制。新组装的病毒颗粒进入唾液或感染附近的B细胞，其中EBV建立终身潜伏感染。病毒潜伏蛋白和裂解蛋白的表达是健康B细胞转化为恶性淋巴增生的原因。在EBV阳性的移植受者中，EBV再活化是一种常见的观察结果。溶解性复制和B细胞中潜伏病毒蛋白的表达以及唾液中EBV DNA的检测是IM和EBV再活化的特征。然而，目前尚不清楚移植受体是否真的脱落了感染性病毒颗粒、缺陷病毒体或仅片段化的EBV DNA。因此，目前尚不清楚这些患者是否具有传染性，代表EBV阴性个体发生PTLD的风险增加。这项研究的目的是分析EB病毒再活化的移植受者的唾液，以确定其所含的EB病毒DNA的来源。为此，我们建议进行定量PCR研究，结合病毒结合和转化试验，以量化唾液中的感染性病毒负荷。这项测试可以很容易地转化为临床实践，并帮助识别高风险患者。在未来的干预性研究中，脱落传染性EBV的患者将被隔离或接受先发制人的治疗，以确定PTLD的降低率。