title: The Epstein-Barr virus DNA load in the peripheral blood of transplant recipients does not accurately reflect the burden of infected cells.
abstract: Transplant recipients frequently exhibit an increased Epstein-Barr virus (EBV) load in the peripheral blood. Here, we quantitated the EBV-infected cells in the peripheral blood of these patients and defined the mode of viral infection, latent or lytic. These data indicated that there is no strong correlation between the number of infected cells and the EBV load (EBVL). This can be explained by a highly variable number of EBV copies per infected cell and by lytic replication in some cells. The plasma of these patients did not contain any free infectious viruses, but contained nevertheless EBV DNA, sometimes in large amounts, that probably originates from cell debris and contributed to the total EBVL. Some of the investigated samples carried a highly variable number of infected cells in active latency, characterized by an expression of the Epstein-Barr nuclear antigens (EBNA2) protein. However, a third of the samples expressed neither EBNA2 nor lytic proteins. Patients with an increased EBVL represent a heterogeneous group of patients whose infection cannot be characterized by this method alone. Precise characterization of the origin of an increased EBVL, in particular, in terms of the number of EBV-infected cells, requires additional investigations including the number of EBV-encoded small RNA-positive cells.
authors.affiliation: German Cancer Research Centre (DKFZ) Unit F100, Heidelberg, Germany.|Institut National de la Santé et de la Recherche Médicale (INSERM) Unit U1074, Heidelberg, Germany.|German center for infection research (DZIF), Heidelberg, Germany.|Nierenzentrum Heidelberg, Heidelberg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Fink
authors.affiliation: German Cancer Research Centre (DKFZ) Unit F100, Heidelberg, Germany.|Institut National de la Santé et de la Recherche Médicale (INSERM) Unit U1074, Heidelberg, Germany.|German center for infection research (DZIF), Heidelberg, Germany.
authors.forename: Ming-Han
authors.initials: MH
authors.lastname: Tsai
authors.affiliation: Center for Infectious Diseases, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Paul
authors.initials: P
authors.lastname: Schnitzler
authors.affiliation: Nierenzentrum Heidelberg, Heidelberg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Zeier
authors.affiliation: Center for Infectious Diseases, Heidelberg University Hospital, Heidelberg, Germany.|Department of Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Dreger
authors.affiliation: Department of Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Wuchter
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Olcay C
authors.initials: OC
authors.lastname: Bulut
authors.affiliation: Children's Hospital Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Uta
authors.initials: U
authors.lastname: Behrends
authors.affiliation: German Cancer Research Centre (DKFZ) Unit F100, Heidelberg, Germany.|Institut National de la Santé et de la Recherche Médicale (INSERM) Unit U1074, Heidelberg, Germany.|German center for infection research (DZIF), Heidelberg, Germany.
authors.forename: Henri-Jacques
authors.initials: HJ
authors.lastname: Delecluse
mesh_terms: D000328:Adult; D000368:Aged; D000956:Antigens, Viral; D001402:B-Lymphocytes / Q000276:immunology; D004279:DNA, Viral / Q000097:blood*; D020031:Epstein-Barr Virus Infections / Q000097:blood*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000378:metabolism; D005260:Female; D004854:Herpesvirus 4, Human; D006801:Humans; D007165:Immunosuppression Therapy; D017404:In Situ Hybridization, Fluorescence; D016030:Kidney Transplantation; D008232:Lymphoproliferative Disorders / Q000821:virology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D033581:Stem Cell Transplantation; D066027:Transplant Recipients; D019562:Viral Load; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D000956:Antigens, Viral; D004279:DNA, Viral; C402641:EBNA-2 protein, Human herpesvirus 4; D019309:Epstein-Barr Virus Nuclear Antigens; D014764:Viral Proteins
keywords: Epstein-Barr virus infection; malignancies and long term compliations after transplantation; post-transplant lymphoproliferative disorders