scholarly journals Localization of Epstein-Barr virus cytotoxic T cell epitopes using recombinant vaccinia: implications for vaccine development.

1992 ◽  
Vol 176 (1) ◽  
pp. 169-176 ◽  
Author(s):  
R Khanna ◽  
S R Burrows ◽  
M G Kurilla ◽  
C A Jacob ◽  
I S Misko ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Vaccine Development ◽  
Nuclear Antigen ◽  
Cytotoxic T Cell ◽  
Effective Vaccine ◽  
Recombinant Vaccinia ◽  
Ctl Epitopes ◽  
Barr Virus ◽  
Epstein Barr

There is considerable interest in designing an effective vaccine to the ubiquitous Epstein-Barr virus (EBV). An important role for EBV-specific cytotoxic T lymphocytes (CTLs) in eliminating virus-infected cells is well established. Limited studies using a small number of immune donors have defined target epitopes within the latent antigens of EBV. The present study provides an extensive analysis of the distribution of class I-restricted CTL epitopes within EBV-encoded proteins. Using recombinant vaccinia encoding individual EBV latent antigens (Epstein-Barr nuclear antigen [EBNA] 1, 2, 3A, 3B, 3C, LP, and LMP 1), we have successfully localized target epitopes recognized by CTL clones from a panel of 14 EBV-immune donors. Of the 20 CTL epitopes localized, five were defined at the peptide level. Although CTL clones specific for nine epitopes recognized both type 1 and type 2 transformants, a significant number of epitopes (7/16 epitopes for which EBV type specificity was determined) were detected only on type 1 EBV transformants. Vaccinia recombinants encoding EBNA 3A and EBNA 3C were recognized more frequently than any other vaccinia recombinants used in this study, while no CTL epitopes were localized in EBNA 1. Surprisingly, epitope specificity for a large number of EBV-specific CTL clones could not be localized, although vaccinia recombinants used in this study encoded most of the latent antigens of EBV. These results suggest that any EBV vaccine based on CTL epitopes designed to provide widespread protection will need to include not only latent antigen sequences but also other regions of the genome. The apparent inability of human CTLs to recognize EBNA 1 as a target antigen, often the only latent antigen expressed in Burkitt's lymphoma and nasopharyngeal carcinoma, suggests that EBV-specific CTL control of these tumors will not be feasible unless the down-regulation of latent antigens can be reversed.

Concomitant nephrotic syndrome and tubulointerstitial nephritis in a child with Epstein-Barr virus mononucleosis

2021 ◽  
Vol 14 (2) ◽  
pp. e240108
Author(s):  
Ratna Acharya ◽  
Xu Zeng ◽  
Kiran Upadhyay
Keyword(s):  
Nephrotic Syndrome ◽  
Epstein Barr Virus ◽  
Cell Activity ◽  
Nuclear Antigen ◽  
Cytotoxic T Cell ◽  
Target Cells ◽  
Tubulointerstitial Injury ◽  
Strong Immune Response ◽  
Barr Virus ◽  
Epstein Barr

Acute kidney injury (AKI) and nephrotic syndrome (NS) are uncommon manifestations of Epstein-Barr virus (EBV) mononucleosis. We report a 4-year-old boy with Infectious mononucleosis (IM) who presented with dialysis-requiring AKI and NS. Renal biopsy showed severe acute tubular necrosis, mild chronic interstitial nephritis and focal podocyte foot processes effacement. EBV early RNA was not detected in the renal tissue. However, immunophenotyping of peripheral lymphocytes showed increased cytotoxic T cell activity and increased memory B cells. Treatment with steroid led to rapid resolution of NS within 3 weeks. Renal function stabilised. EBV viral capsid antigen (VCA) IgM remained elevated until 4 months before starting to decline when VCA IgG and nuclear antigen started appearing. B lymphocytes are the predominant target cells in EBV infection and additionally may also act as antigen presenting cells to T lymphocytes, thereby eliciting the strong immune response and leading to podocyte and tubulointerstitial injury.

scholarly journals Dominant selection of an invariant T cell antigen receptor in response to persistent infection by Epstein-Barr virus.

1994 ◽  
Vol 180 (6) ◽  
pp. 2335-2340 ◽  
Author(s):  
V P Argaet ◽  
C W Schmidt ◽  
S R Burrows ◽  
S L Silins ◽  
M G Kurilla ◽  
...  
Keyword(s):  
T Cell ◽  
Persistent Infection ◽  
Epstein Barr Virus ◽  
Nuclear Antigen ◽  
Cytotoxic T Cell ◽  
Beta Chain ◽  
Memory Response ◽  
Barr Virus ◽  
Epstein Barr ◽  
Selection Of

To examine T cell receptor (TCR) diversity involved in the memory response to a persistent human pathogen, we determined nucleotide sequences encoding TCR-alpha and -beta chains from HLA-B8-restricted, CD8+ cytotoxic T cell clones specific for an immunodominant epitope (FLRGRAYGL) in Epstein-Barr virus (EBV) nuclear antigen 3. Herein, we show that identical TCR protein sequences are used by clones from each of four healthy unrelated virus carriers; a clone from a fifth varied conservatively at only two residues. This dominant selection of alpha and beta chain rearrangements suggest that a persistent viral infection can select for a highly focused memory response and indicates a strong bias in gene segment usage and recombination. A novel double-step semiquantitative polymerase chain reaction (PCR) procedure and direct sequencing of amplified TCR cDNA from fresh lymphocytes derived from three HLA-B8 individuals detected transcripts specific for the conserved beta chain in an EBV-seropositive donor but not in two seronegative donors. This report describes an unprecedented degree of conservation in TCR selected in response to a natural persistent infection.

scholarly journals Latent Gene Sequencing Reveals Familial Relationships among Chinese Epstein-Barr Virus Strains and Evidence for Positive Selection of A11 Epitope Changes

2003 ◽  
Vol 77 (21) ◽  
pp. 11517-11530 ◽  
Author(s):  
R. S. Midgley ◽  
A. I. Bell ◽  
D. J. McGeoch ◽  
A. B. Rickinson
Keyword(s):  
Epstein Barr Virus ◽  
Sequence Divergence ◽  
Nuclear Antigen ◽  
Coding Region ◽  
Immune Selection ◽  
Genomic Context ◽  
Barr Virus ◽  
Epstein Barr

ABSTRACT Epstein-Barr virus (EBV) strains from the highly HLA-A11-positive Chinese population are predominantly type 1 and show a variety of sequence changes (relative to the contemporary Caucasian prototype strain B95.8) in the nuclear antigen EBNA3B sequences encoding two immunodominant HLA-A11 epitopes, here called IVT and AVF. This has been interpreted by some as evidence of immune selection and by others as random genetic drift. To study epitope variation in a broader genomic context, we sequenced the whole of EBNA3B and parts of the EBNA2, 3A, and 3C genes from each of 31 Chinese EBV isolates. At each locus, type 1 viruses showed <2% nucleotide divergence from the B95.8 prototype while type 2 sequences remained even closer to the contemporary African prototype Ag876. However, type 1 isolates could clearly be divided into families based on linked patterns of sequence divergence from B95.8 across all four EBNA loci. Different patterns of IVT and AVF variation were associated with the different type 1 families, and there was additional epitope diversity within families. When the EBNA3 gene sequences of type 1 Chinese strains were subject to computer-based analysis, particular codons within the A11-epitope-coding region were among the few identified as being under positive or diversifying selection pressure. From these results, and the observation that mutant epitopes are consistently nonimmunogenic in vivo, we conclude that the immune selection hypothesis remains viable and worthy of further investigation.

scholarly journals T cell responses and virus evolution: loss of HLA A11-restricted CTL epitopes in Epstein-Barr virus isolates from highly A11-positive populations by selective mutation of anchor residues.

1994 ◽  
Vol 179 (4) ◽  
pp. 1297-1305 ◽  
Author(s):  
P O de Campos-Lima ◽  
V Levitsky ◽  
J Brooks ◽  
S P Lee ◽  
L F Hu ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Cytotoxic T Lymphocyte ◽  
Virus Evolution ◽  
Nuclear Antigen ◽  
Ctl Epitopes ◽  
Barr Virus ◽  
Southern Chinese ◽  
Epstein Barr ◽  
Ctl Responses

Epstein-Barr virus (EBV) is a B lymphotropic herpesvirus of humans that elicits strong HLA class I-restricted cytotoxic T lymphocyte (CTL) responses. An influence of such responses on virus evolution was first suggested by our finding that EBV isolates from the highly HLA A11-positive Papua New Guinea (PNG) population carried a lys-thr mutation at residue 424 of the nuclear antigen EBV-encoded nuclear antigen (EBNA4) that destroyed the immunodominant target epitope for A11-restricted CTL recognition. Here we turn to a much larger population, Southern Chinese, where the A11 allele is again present in over 50% of the individuals. Each of 23 EBV isolates analyzed from this population were also mutated in the EBNA4 416-424 epitope, the mutations selectively involving one of the two anchor residues in positions 2 (417 val-leu) or 9 (424 lys-asp, -arg or -thr) that are critical for A11-peptide interaction. The majority of the Chinese isolates and all 10 PNG isolates also carried mutations affecting positions 1 and 2 of the next most immunodominant A11-restricted epitope, EBNA4 residues 399-408. These changes clearly affected antigenicity since A11-positive lymphoblastoid cell lines (LCLs) carrying these mutant EBV strains were not recognized by A11-restricted CTLs raised against the prototype B95.8 virus. Furthermore, Chinese donors naturally infected with these mutant viruses did not mount detectable A11-restricted CTL responses on in vitro stimulation with autologous LCL cells carrying either the B95.8 or their endogenous EBV strain. In two different highly A11-positive populations, therefore, immune pressure appears to have selected for resident EBV strains lacking immunodominant A11-restricted CTL epitopes.

High frequency of co-infection by Epstein–Barr virus types 1 and 2 in patients with multiple sclerosis

2011 ◽  
Vol 17 (11) ◽  
pp. 1295-1300 ◽  
Author(s):  
Almudena Santón ◽  
Eva Cristóbal ◽  
María Aparicio ◽  
Ana Royuela ◽  
Luisa M. Villar ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Epstein Barr Virus ◽  
Nuclear Antigen ◽  
Molecular Evidence ◽  
Specific Sequence ◽  
Logistic Regression Models ◽  
Barr Virus ◽  
Type Assignment ◽  
Epstein Barr

Background: The existence of Epstein–Barr virus (EBV) strains specifically associated with multiple sclerosis (MS) is a matter of controversy. Little is also known about the prevalence of EBV types 1 and 2 in MS patients and the presence of co-infections by both strains. Objective: To make EBV strain type assignment and compare the frequencies of types 1, 2 and co-infections by both in MS patients and healthy controls. Methods: Blood samples from 75 consecutive MS patients and 186 controls were collected. EBV was simultaneously detected and typed using a polymerase chain reaction (PCR) which amplified a strain-specific sequence in the EBV nuclear antigen 2. Results: EBV was detected in 70 out of 75 patients (93.3%) and in 123 of 186 controls (66.1%). Among positive cases, type 1 was found in 6 patients (8.6%) and 40 controls (32.5%), type 2 in 1 patient (1.4%) and 37 controls (30.1%), and dual-infections by both EBV types were detected in 63 patients (90%) and 46 controls (37.4%). Logistic regression models showed that MS was significantly associated with the presence of EBV ( p < 0.001) and also with dual type infections ( p < 0.001). Conclusion: This study provides molecular evidence associating co-infection of type 1 and 2 EBV with MS.

Epstein-Barr virus nuclear antigen type 1 binding: electron microscopy

1988 ◽  
Vol 22 (2-3) ◽  
pp. 133-142 ◽  
Author(s):  
I. Hirsch ◽  
J. Reischig ◽  
O. Benada ◽  
D. Bartsch ◽  
B. Břicháček ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Epstein Barr Virus ◽  
Nuclear Antigen ◽  
Barr Virus ◽  
Epstein Barr

scholarly journals HLA-A11-Restricted Epitope Polymorphism among Epstein-Barr Virus Strains in the Highly HLA-A11-Positive Chinese Population: Incidence and Immunogenicity of Variant Epitope Sequences

2003 ◽  
Vol 77 (21) ◽  
pp. 11507-11516 ◽  
Author(s):  
R. S. Midgley ◽  
A. I. Bell ◽  
Q. Y. Yao ◽  
D. Croom-Carter ◽  
A. D. Hislop ◽  
...  
Keyword(s):  
Chinese Population ◽  
Epstein Barr Virus ◽  
Cytotoxic T Lymphocyte ◽  
Nuclear Antigen ◽  
Sequence Variants ◽  
Barr Virus ◽  
Epstein Barr

ABSTRACT An individual's CD8+-cytotoxic-T-lymphocyte (CTL) response to Epstein-Barr virus (EBV) latent cycle antigens focuses on a small number of immunodominant epitopes often presented by just one of the available HLA class I alleles; for example, HLA-A11-positive Caucasians frequently respond to two immunodominant HLA A11 epitopes, IVTDFSVIK (IVT) and AVFDRKSDAK (AVF), within the nuclear antigen EBNA3B. Here, we reexamine the spectrum of EBV strains present in the highly HLA-A11-positive Chinese population for sequence changes in these epitopes relative to the Caucasian type 1 prototype strain B95.8. The IVT epitope was altered in 61 of 64 Chinese type 1 viruses, with four different sequence variants being observed, and the AVF epitope was altered in 46 cases with six different sequence variants; by contrast, all 10 Chinese type 2 viruses retained the prototype 2 epitope sequences. All but one of the type 1 epitope variants were poorly recognized by IVT- or AVF-specific CTLs in pulse-chase assays of peptide-mediated target cell lysis. More importantly, we screened HLA-A11-positive Chinese donors carrying viruses with known epitope mutations for evidence of epitope-specific CTL memory by enzyme-linked immunospot assays: none of the type 1 variants tested, nor the type 2 prototype, appeared to be immunogenic in vivo. The data remain consistent with the possibility that, during virus-host coevolution, pressure from the host CTL-mediated immune response has given A11 epitope-loss viruses a selective advantage.

scholarly journals Five new cytotoxic T cell epitopes identified within Epstein-Barr virus nuclear antigen 3

1994 ◽  
Vol 75 (9) ◽  
pp. 2489-2493 ◽  
Author(s):  
S. R. Burrows ◽  
J. Gardner ◽  
R. Khanna ◽  
T. Steward ◽  
D. J. Moss ◽  
...  
Keyword(s):  
T Cell ◽  
Epstein Barr Virus ◽  
Nuclear Antigen ◽  
Cytotoxic T Cell ◽  
T Cell Epitopes ◽  
Barr Virus ◽  
Epstein Barr
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