Epstein-Barr Virus (EBV) DNA in Plasma Is Not Encapsidated in Patients With EBV-Related Malignancies

Abstract

Epstein-Barr Virus (EBV), a ubiquitous gamma herpes virus, infects more than 95% of the human population before adulthood. Life-long persistence, usually without adverse health consequences, relies on a balance between viral latency, viral replication, and host immune response. Patients with EBV-related disease often have high levels of EBV DNA in their plasma. This study addresses whether this circulating, cell-free EBV DNA is encapsidated in virions or exists as naked genomes. First, an assay was developed, combining DNase I and quantitative real-time PCR, to discriminate encapsidated from naked EBV DNA. EBV DNA was almost always naked in the plasma of AIDS-related lymphoma patients (n = 11) and immunosuppressed/posttransplantation patients (n = 8). In contrast, infectious mononucleosis patients (n = 30) often had a mixture of encapsidated and naked EBV DNA. These findings may be important in understanding how viral load relates to disease status and in predicting response to nucleoside analogs and other antiviral therapies.

Measuring Epstein–Barr virus (EBV) load: the significance and application for each EBV‐associated disease

“…Some transformed B cells in latent infection leak into the bloodstream. Encapsidated viral genomes (virions), which are produced from plasma cells in lytic infection, flow into the peripheral blood [48]. Fragmented or naked DNA from apoptotic cells may also be detected as cell-free EBV DNA in the peripheral blood.…”

“…Most EBV is cell-associated and EBV DNA is detected in high copy numbers in PBMCs (Figure 2). Cell-free, non-encapsidated EBV DNA is also detected in the blood, indicating fragmented or naked DNA [48]. Riddler et al were the first to show that molecular testing for EBV in the peripheral blood could be used to non-invasively monitor PTLD [34].…”

TLR9 triggering in Burkitt's lymphoma cell lines suppresses the EBV BZLF1 transcription via histone modification

“…To investigate whether TLR9 suppresses virus production, we measured EBV DNA copy numbers in the supernatant of Akata cells. Non-encapsidated EBV DNA is sensitive to DNAse and therefore does not originate from lytic infection but rather from dying latently infected cells (Ryan et al, 2004). Thus, DNAse treatment was used to detect only encapsidated virus, for example, virus produced from lytic infection.…”

Epstein-Barr virus DNA in serum as an early prognostic marker in children and adolescents with Hodgkin lymphoma

“…20,21 Similar but less extensive investigations suggest that EBV DNA in cell-free blood from patients with HL is also tumor derived. 7 The results presented here suggest that cell-free EBV DNA in blood is a tumor marker in EBV-associated HL. At baseline, the presence of EBV in pediatric HL did not have prognostic significance, but the presence of EBV DNA at 8 days after the initiation of therapy seems to identify patients with an inadequate response to treatment.…”

“…We also sought to determine whether the presence of EBV cell-free DNA after the initiation of therapy would have prognostic value. 4,[7][8][9] To address these questions, we used specimens collected at baseline and at 8 days after the initiation of chemotherapy in a subset of patients with intermediate-risk classical HL enrolled in Children's Oncology Group (COG) AHOD0031. …”