Abstract
The ZEBRA protein (encoded by the BZLF1 gene), is the major transcription factor of EBV, expressed upon EBV lytic cycle activation. Several studies highlighted the critical role of EBV lytic infection as a risk factor for lymphoproliferative disorders like post-transplant lymphoproliferative disease (PTLD). Here, we use an antigen-capture ELISA assay specifically designed to detecting the circulating soluble ZEBRA (sZEBRA) in serum samples (threshold value determined at 40ng/mL). We retrospectively investigated a population of 66 transplanted patients comprising 35 PTLD. All the samples from a control population (30 EBV-seronegative subjects and 25 immunocompetent individuals with EBV serological reactivation), classified as sZEBRA < 40ng/mL were assigned as negative. At PTLD diagnosis, EBV genome (quantified by qPCR with EBV DNA>200 copies/mL) and sZEBRA were detectable in 51% and 60% of cases, respectively. In the patients who developed a pathologically-confirmed PTLD, the mean sZEBRA value in cases, was 399 ng/mL +/− 141 versus 53ng/mL +/− 7 in patients who did not (p < 0,001). This is the first report relating to the detection of the circulating ZEBRA in serum specimens, as well as the first analysis dealing with the lytic cycle of EBV in PTLD patients with this new biomarker.
Highlights
Epstein–Barr virus (EBV) is a human herpesvirus that causes infectious mononucleosis
AZ130 specific for ZEBRA protein were employed in a sandwich ELISA throughout the whole procedure for quantifying captured soluble ZEBRA (sZEBRA) (Fig. S1)
The follow-up panel in Figure S5 illustrates the kinetics of EBV load and sZEBRA in sera from patients prior the post-transplant lymphoproliferative disease (PTLD) episode. It is worth noticing the precocity of sZEBRA compared with EBV DNA. This is the first report pertaining to the detection of a soluble form of the ZEBRA protein in serum specimens, as well as the first analysis on the replicative nature of EBV by using this putative new biomarker in PTLD patients
Summary
Epstein–Barr virus (EBV) is a human herpesvirus that causes infectious mononucleosis. In PTLD patients, the increased EBV load in mononuclear cells (PBMCs) of the peripheral blood can be accounted for by an increased number of circulating EBV-positive cells. These cells represent memory B-cells rather than proliferating lymphoblast cells, and thereby resemble latently-infected resting B-cells, with a restricted set of EBV latency genes[2, 8, 9]. As ZEBRA was reported able to activate host cellular genes[20,21,22,23,24], the reactivation of EBV lytic cycle was shown to contribute to the growth of latently-infected cells[14, 16] and this, by promoting the release of paracrine B-cell growth factors[25]. Our research revealed that this protein, usually found in the nucleus of EBV-infected cells, was detected in the serum of patients suffering from EBV-associated diseases
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
