The Biology and Clinical Utility of EBV Monitoring in Blood

Abstract

Epstein-Barr virus (EBV) DNA in blood can be quantified in peripheral blood mononuclear cells, in circulating cell-free (CCF) DNA specimens, or in whole blood. CCF viral DNA may be actively released or extruded from viable cells, packaged in virions or passively shed from cells during apoptosis or necrosis. In infectious mononucleosis, viral DNA is detected in each of these kinds of specimens, although it is only transiently detected in CCF specimens. In nasopharyngeal carcinoma, CCF EBV DNA is an established tumor marker. In EBV-associated Hodgkin lymphoma and in EBV-associated extranodal NK-/T-cell lymphoma, there is growing evidence for the utility of CCF DNA as a tumor marker.

Epstein‐Barr viral load monitoring for diagnosing post‐transplant lymphoproliferative disorder in pediatric liver transplant recipients

“…Recent studies advocated the quantitation of EBV DNA in plasma instead of whole blood suggesting the utility of EBV DNA in plasma as a predictor for EBV‐associated malignancies including lymphoma and nasopharyngeal carcinoma, and a surrogate marker for assessing EBV reactivation dynamics and response to treatment . Furthermore, no significant correlation existed between whole blood and plasma.…”

High pretreatment plasma Epstein‐Barr virus (EBV) DNA level is a poor prognostic marker in HIV‐associated, EBV‐negative diffuse large B‐cell lymphoma in Malawi

“…Plasma EBV has been studied intensely for its clinical utility as a predictive or prognostic biomarker in EBV‐driven lymphoma . In SSA, this biomarker has been most extensively evaluated in endemic Burkitt lymphoma and classic Hodgkin lymphoma, both of which are EBV positive in most cases .…”

“…Latently infected cells are rare in normal individuals, representing fewer than 1 in 10,000 peripheral blood leukocytes . As a result, EBV DNA is typically undetectable or present only at a very low level in the plasma of normal adults . In patients with EBV‐driven malignancies, particularly in the post‐transplant setting, plasma EBV may rise as a ctDNA marker .…”

Persistent KSHV Infection Increases EBV-Associated Tumor Formation In Vivo via Enhanced EBV Lytic Gene Expression

“…Indeed, early EBV lytic transcripts and antigens, such as BZLF1, have been previously reported in dually infected PELs and PEL cell lines (Cannon et al, 2000;Horenstein et al, 1997). Furthermore, EBV copy numbers in circulating cell-free (CCF) DNA, which is a surrogate marker for lytic EBV replication, has been found to correlate well with EBV-associated malignancy burden, risk to develop EBV-positive lymphomas in immune-suppressed conditions, and EBV-associated tumor relapse after treatment (Kanakry and Ambinder, 2015). As such, rising EBV copy numbers in CCF DNA of bone marrow transplant patients predict the development of post-transplant lymphoproliferative disease and can be used as an indication to start B cell-depleting therapy to decrease the risk of lymphoma formation (van Esser et al, 2001(van Esser et al, , 2002.…”