EBNA1 distorts oriP, the Epstein-Barr virus latent replication origin.

ABSTRACT Latent Epstein-Barr virus (EBV) is maintained by the virus replication origin oriP that initiates DNA replication with the viral oriP-binding factor EBNA1. However, it is not known whether oriP's replicator activity is regulated by virus proteins or extracellular signals. By using a transient replication assay, we found that a low level of expression of viral signal transduction activator latent membrane protein 1 (LMP1) suppressed oriP activity. The binding site of the tumor necrosis factor receptor-associated factor (TRAF) of LMP1 was essential for this suppressive effect. Activation of the TRAF signal cascade by overexpression of TRAF5 and/or TRAF6 also suppressed oriPactivity. Conversely, blocking of TRAF signaling with dominant negative mutants of TRAF5 and TRAF6, as well as inhibition of a downstream signal mediator p38 MAPK, released the LMP1-inducedoriP suppression. Furthermore, activation of TRAF6 signal cascade by lipopolysaccharides (LPS) resulted in loss of EBV from Burkitt's lymphoma cell line Akata, and inhibition of p38 MAPK abolished the suppressive effect of LPS. These results suggested that the level of oriP activity is regulated by LMP1 and extracellular signals through TRAF5- and TRAF6-mediated signal cascades.

Download Full-text

Epstein-Barr nuclear antigen 1 mediates a DNA loop within the latent replication origin of Epstein-Barr virus.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.88.23.10875 ◽

1991 ◽

Vol 88 (23) ◽

pp. 10875-10879 ◽

Cited By ~ 75

Author(s):

L. Frappier ◽

M. O'Donnell

Keyword(s):

Replication Origin ◽

Epstein Barr Virus ◽

Nuclear Antigen ◽

Barr Virus ◽

Dna Loop ◽

Epstein Barr ◽

Epstein Barr Nuclear Antigen

Download Full-text

The Dyad Symmetry Element of Epstein-Barr Virus Is a Dominant but Dispensable Replication Origin

PLoS ONE ◽

10.1371/journal.pone.0018609 ◽

2011 ◽

Vol 6 (5) ◽

pp. e18609 ◽

Cited By ~ 11

Author(s):

Elisabeth Ott ◽

Paolo Norio ◽

Marion Ritzi ◽

Carl Schildkraut ◽

Aloys Schepers

Keyword(s):

Replication Origin ◽

Epstein Barr Virus ◽

Symmetry Element ◽

Barr Virus ◽

Epstein Barr ◽

Dyad Symmetry

Download Full-text

A Quantitative Ultrastructural Study of Peripheral Blood Lymphocytes Containing Parallel Tubular Arrays in Epstein-Barr Virus and Cytomegalo-Virus Mononucleosis

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100098769 ◽

1981 ◽

Vol 39 ◽

pp. 454-455

Author(s):

C. M. Payne ◽

P. M. Tennican

Keyword(s):

Peripheral Blood ◽

Lymphocyte Count ◽

Epstein Barr Virus ◽

Absolute Lymphocyte Count ◽

Peripheral Blood Lymphocytes ◽

Clinical State ◽

Barr Virus ◽

The Absolute ◽

Epstein Barr ◽

Tubular Arrays

In the normal peripheral circulation there exists a sub-population of lymphocytes which is ultrastructurally distinct. This lymphocyte is identified under the electron microscope by the presence of cytoplasmic microtubular-like inclusions called parallel tubular arrays (PTA) (Figure 1), and contains Fc-receptors for cytophilic antibody. In this study, lymphocytes containing PTA (PTA-lymphocytes) were quantitated from serial peripheral blood specimens obtained from two patients with Epstein -Barr Virus mononucleosis and two patients with cytomegalovirus mononucleosis. This data was then correlated with the clinical state of the patient.It was determined that both the percentage and absolute number of PTA- lymphocytes was highest during the acute phase of the illness. In follow-up specimens, three of the four patients' absolute lymphocyte count fell to within normal limits before the absolute PTA-lymphocyte count.In one patient who was followed for almost a year, the absolute PTA- lymphocyte count was consistently elevated (Figure 2). The estimation of absolute PTA-lymphocyte counts was determined to be valid after a morphometric analysis of the cellular areas occupied by PTA during the acute and convalescent phases of the disease revealed no statistical differences.

Download Full-text

Studies of Epstein-Barr Virus Antigens Using Immunoperoxidase and Immunofluorescence Techniques

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010011533x ◽

1975 ◽

Vol 33 ◽

pp. 342-343

Author(s):

R. Stephens ◽

K. Traul ◽

D. Woolf ◽

P. Gaudreau

Keyword(s):

Electron Microscopy ◽

Nasopharyngeal Carcinoma ◽

Epstein Barr Virus ◽

Barr Virus ◽

If Technique ◽

Infected Cells ◽

Virus Antigens ◽

Epstein Barr ◽

Virus Capsid Antigen ◽

Antigen Reactivity

A number of antigens have been found associated with persistent EBV infections of lymphoblastoid cells. Identification and localization of these antigens were principally by immunofluorescence (IF) techniques using sera from patients with nasopharyngeal carcinoma (NPC), Burkitt lymphoma (BL), and infectious mononucleosis (IM). Our study was mainly with three of the EBV related antigens, a) virus capsid antigen (VCA), b) membrane antigen (MA), and c) early antigens (EA) using immunoperoxidase (IP) techniques with electron microscopy (EM) to elucidate the sites of reactivity with EBV and EBV infected cells.Prior to labeling with horseradish peroxidase (HRP), sera from NPC, IM, and BL cases were characterized for various reactivities by the indirect IF technique. Modifications of the direct IP procedure described by Shabo and the indirect IP procedure of Leduc were made to enhance penetration of the cells and preservation of antigen reactivity.

Download Full-text