Functional mapping of the Epstein-Barr virus genome: Identification of sites coding for the restricted early antigen, the diffuse early antigen, and the nuclear antigen

Virology ◽  
1983 ◽  
Vol 129 (1) ◽  
pp. 188-198 ◽  
Author(s):  
Ronald Glaser ◽  
Ann Boyd ◽  
Jay Stoerker ◽  
Jane Holliday
Keyword(s):  
Epstein Barr Virus ◽  
Virus Genome ◽  
Functional Mapping ◽  
Nuclear Antigen ◽  
Early Antigen ◽  
Barr Virus ◽  
Epstein Barr

Encephalitis in Infectious Mononucleosis: Diagnostic Considerations

PEDIATRICS ◽  
1976 ◽  
Vol 58 (6) ◽  
pp. 877-880
Author(s):  
Beverly J. Lange ◽  
Peter H. Berman ◽  
Joseph Bender ◽  
Werner Henle ◽  
John F. Hewetson
Keyword(s):  
Infectious Mononucleosis ◽  
Epstein Barr Virus ◽  
Nuclear Antigen ◽  
Diffuse Component ◽  
Early Antigen ◽  
Barr Virus ◽  
Ebv Infection ◽  
Antibody Titers ◽  
Epstein Barr ◽  
Etiologic Diagnosis

Four atypical cases of presumed infectious mononucleosis (IM) encephalitis are presented. To establish an etiologic diagnosis, Paul-Bunnell-Davidsohn heterophil titers (PBD), antibody titers to the antigens of the Epstein-Barr virus (EBV), and oropharyngeal excretion of EBV were determined. Criteria for a primary EBV infection are (1) an antiviral capsid antigen titer of 1:160 or greater, (2) the presence of antibody to the diffuse component of the early antigen, (3) absence of antibody to the nuclear antigen, and (4) excretion of the virus from the oropharynx. Three of the four cases met these criteria; of the three, one did not have a positive heterophil titer. The fourth case turned out not to be IM; there was a positive PBD heterophil, but there was no evidence of primary EBV infection. Although the PBD heterophil is usually a reliable test to diagnosis IM, it is not always present in children, and it is sometimes nonspecifically elevated. Some EBV titers can be nonspecifically elevated as well; however, the above criteria are diagnostic of primary EBV infection.

scholarly journals The Replicator of the Epstein-Barr Virus Latent Cycle Origin of DNA Replication, oriP, Is Composed of Multiple Functional Elements

2001 ◽  
Vol 75 (22) ◽  
pp. 10582-10592 ◽  
Author(s):  
Michelle D. Koons ◽  
Sarah Van Scoy ◽  
Janet Hearing
Keyword(s):  
Binding Sites ◽  
Epstein Barr Virus ◽  
Protein S ◽  
Virus Genome ◽  
Nuclear Antigen ◽  
Cell Protein ◽  
Present Evidence ◽  
Replication Assay ◽  
Barr Virus ◽  
Epstein Barr

ABSTRACT Replication of the Epstein-Barr virus genome initiates at one of several sites in latently infected, dividing cells. One of these replication origins is close to the viral DNA maintenance element, and, together, this replication origin and the maintenance element are referred to as oriP. The replicator oforiP contains four binding sites for Epstein-Barr virus nuclear antigen 1 (EBNA-1), the sole viral protein required for the replication and maintenance of oriP plasmids. We showed previously that these EBNA-1 sites function in pairs and that mutational inactivation of one pair does not eliminate replicator function. In this study we characterized the contribution of each EBNA-1 site within the replicator and flanking sequences through the use of an internally controlled replication assay. We present evidence that shows that all four EBNA-1 sites are required for anoriP plasmid to be replicated in every cell cycle. Results from these experiments also show that the paired EBNA-1 binding sites are not functionally equivalent and that the low affinity of sites 2 and 3 compared to that of sites 1 and 4 is not essential for replicator function. Our results suggest that a host cell protein(s) binds sequences flanking the EBNA-1 sites and that interactions between EBNA-1 and this protein(s) are critical for replicator function. Finally, we present evidence that shows that the minimal replicator oforiP consists of EBNA-1 sites 3 and 4 and two copies of a 14-bp repeat that is present in inverse orientation flanking these EBNA-1 sites. EBNA-1 sites 1 and 2, together with an element(s) within nucleotides 9138 to 9516, are ancillary elements required for full replicator activity.

scholarly journals Initiation of latent DNA replication in the Epstein-Barr virus genome can occur at sites other than the genetically defined origin.

1995 ◽  
Vol 15 (5) ◽  
pp. 2893-2903 ◽  
Author(s):  
R D Little ◽  
C L Schildkraut
Keyword(s):  
Mammalian Cells ◽  
Epstein Barr Virus ◽  
Virus Genome ◽  
Replication Initiation ◽  
Nuclear Antigen ◽  
Replication Forks ◽  
Small Plasmid ◽  
Barr Virus ◽  
Latently Infected ◽  
Epstein Barr

Our laboratory has previously shown that replication of a small plasmid, p174, containing the genetically defined Epstein-Barr virus (EBV) latent origin of replication, oriP, initiates within oriP at or near a dyad symmetry (DS) element and terminates specifically at a family of repeated sequences (FR), also located within oriP. We describe here an analysis of the replication of intact approximately 170-kb EBV genomes in four latently infected cell lines that uses two-dimensional gel replicon mapping. Initiation was detected at oriP in all EBV genomes examined; however, some replication forks appear to originate from alternative initiation sites. In addition, pausing of replication forks was observed at the two clusters of EBV nuclear antigen 1 binding sites within oriP and at or near two highly expressed viral genes 0.5 to 1 kb upstream of oriP, the EBV-encoded RNA (EBER) genes. In the Raji EBV genome, the relative abundance of these stalled forks and the direction in which they are stalled indicate that most replication forks originate upstream of oriP. We thus searched for additional initiation sites in the Raji EBV and found that the majority of initiation events were distributed over a broad region to the left of oriP. This delocalized pattern of initiation resembles initiation of replication in several well-characterized mammalian chromosomal loci and is the first described for any viral genome. EBV thus provides a unique model system with which to investigate factors influencing the selection of replication initiation and termination sites in mammalian cells.

scholarly journals Antibodies against Epstein–Barr virus gp78 antigen: a novel marker for serological diagnosis of nasopharyngeal carcinoma detected by xMAP technology

2008 ◽  
Vol 89 (5) ◽  
pp. 1152-1158 ◽  
Author(s):  
Ai-Di Gu ◽  
Yan-Bo Xie ◽  
Hao-Yuan Mo ◽  
Wei-Hua Jia ◽  
Miao-Yan Li ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Sensitivity And Specificity ◽  
Epstein Barr Virus ◽  
Simultaneous Detection ◽  
Nuclear Antigen ◽  
Early Antigen ◽  
Predictive Values ◽  
Barr Virus ◽  
Epstein Barr ◽  
Xmap Technology

Immunoglobulin (Ig) A and/or IgG reactivities to several Epstein–Barr virus (EBV) antigens have been used to facilitate diagnosis of nasopharyngeal carcinoma (NPC). However, antibodies against gp78, an EBV membrane glycoprotein, have not been examined to this day. In this study, we utilized Luminex multi-analyte profiling (xMAP) technology to analyse antibody responses to a synthetic peptide of gp78 in sera samples from 95 NPC patients and 91 healthy controls. Our results showed the sensitivity and specificity of IgA-gp78 for NPC diagnosis were 79 and 71 %, respectively, while those of IgG-gp78 were 74 and 73 %, respectively. The IgA and IgG responses to different EBV antigens were not identical within an individual and IgA-gp78 and IgG-gp78 could be complementary to antibodies against viral capsid antigen (VCA), the diffused early antigen (EA-D) and the nuclear antigen EBNA1 for NPC diagnosis. When the six EBV parameters for NPC prediction, i.e. IgA-gp78, IgG-gp78, IgA-VCA, IgA-EBNA1, IgA-EA-D and IgG-EA-D, are combined, the combined predictors were able to reach overall sensitivity and specificity of 91 and 95 %, respectively. Thus, simultaneous detection of these EBV serological markers could improve the predictive values of NPC using xMAP technology.

scholarly journals Performance of Two Commercially Available Automated Immunoassays for the Determination of Epstein-Barr Virus Serological Status

2012 ◽  
Vol 19 (6) ◽  
pp. 929-934 ◽  
Author(s):  
J. Lupo ◽  
R. Germi ◽  
T. Semenova ◽  
M. Buisson ◽  
J. M. Seigneurin ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Nuclear Antigen ◽  
Viral Capsid Antigen ◽  
Early Antigen ◽  
Barr Virus ◽  
Serological Status ◽  
Individual Marker ◽  
Epstein Barr ◽  
Epstein Barr Nuclear Antigen

ABSTRACTThis study evaluated the performance of two automated Vidas (V) and Liaison (L) immunoassays for Epstein-Barr virus (EBV) serology. The detection of the viral capsid antigen (VCA) IgM, the VCA/early antigen (VCA/EA) IgG, and the Epstein-Barr nuclear antigen (EBNA) IgG was assessed on 526 sera collected for routine EBV testing in immunocompetent subjects. The determination of expected EBV status (186 EBV primary infections, 183 past EBV infections, and 157 EBV-seronegative individuals) was based on results of routine laboratory enzyme immunoassays (EIAs) together with clinical data. The sensitivity and specificity of each individual marker were determined in comparison to the expected EBV status. The agreement between the V and L profiles and the expected EBV status was established through the interpretation of combinations of the different EBV markers. Statistically significant differences between the two tests were found for the specificity of the VCA IgM marker (96.2% for V versus 93.2% for L), the sensitivity of the VCA/EA IgG marker (89% for V versus 94% for L), and the specificity of the EBNA IgG marker (96.5% for V versus 74.2% for L). The results determined for the two assays with respect to overall agreement with the established expected EBV status were not significantly different (89.7% for V versus 88.2% for L), with discrepancies mainly observed in sera referenced as primary infections. These findings demonstrated the similar performances of the Vidas and the Liaison assays for the establishment of an EBV serological status using the VCA, EA, and EBNA markers.

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