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

爱泼斯坦-巴尔病毒（EBV）感染了绝大多数人，通常没有临床后果。如果感染延迟到青春期，传染性单核细胞增多症（IM）综合征可以发展。EBV约占全球所有肿瘤的2%，包括淋巴瘤和癌。免疫缺陷，例如移植携带者，已被确定为ebv阳性移植后淋巴增生性疾病（PTLD）发展的主要危险因素。PTLDs占所有移植后恶性肿瘤的10%，在所有病例中约60%与EBV感染相关。移植后EBV原发感染仍然是PTLD发展的一个重要危险因素。EBV通过唾液经口传播，据信首先感染发生裂解复制的上皮细胞。新组装的病毒颗粒进入唾液或感染附近的B细胞，EBV在其中建立终身潜伏感染。病毒潜伏蛋白和裂解蛋白的表达是健康B细胞向恶性淋巴细胞增殖转化的原因。EBV再激活在EBV阳性移植受者中是一个常见的观察。唾液中B细胞的裂解复制和潜伏病毒蛋白的表达以及EBV DNA的检测是IM和EBV再激活的特征。然而，尚不清楚移植受者是否真的排出了感染性病毒颗粒、缺陷病毒粒子或仅片段化的EBV DNA。因此，尚不清楚这些患者是否具有传染性，这意味着ebv阴性个体发展为PTLD的风险增加。该研究旨在分析EBV再激活移植受者的唾液，以确定其包含的EBV 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来定量唾液中的感染性病毒载量。该检测可以很容易地转化为临床实践，并有助于识别高危患者。在未来的介入研究中，传染性EBV患者将被隔离或接受先发制人的治疗，以确定PTLD的降低率。

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.