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

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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.