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 An Epstein-Barr virus-specific cytotoxic T cell epitope in EBV nuclear antigen 3 (EBNA 3).

1990 ◽  
Vol 171 (1) ◽  
pp. 345-349 ◽  
Author(s):  
S R Burrows ◽  
T B Sculley ◽  
I S Misko ◽  
C Schmidt ◽  
D J Moss
Keyword(s):  
Epstein Barr Virus ◽  
Cell Epitope ◽  
Nuclear Antigen ◽  
Cytotoxic T Cell ◽  
Target Cells ◽  
T Cell Epitope ◽  
Barr Virus ◽  
Nuclear Antigens ◽  
Target Epitope ◽  
Epstein Barr

Epstein-Barr virus (EBV)-specific CTL clones were isolated that recognized A-type EBV transformants but not B-type transformants. These A-type-specific CTL clones (HLA B8 restricted) were used to screen peptides derived from the EBV nuclear antigens (EBNAs) 2, 3, 4, and 6 as potential CTL epitopes. Of the 76 peptides screened, one sequence from EBNA 3 (residues 329-353) was recognized by A-type-specific CTL clones after absorption onto target cells (either autologous B-type transformants or PHA blasts). This report is the first description of an EBV target epitope recognized by specific CTL clones.

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 CD4+ T-Cell Responses to Epstein-Barr Virus Nuclear Antigen EBNA1 in Chinese Populations Are Highly Focused on Novel C-Terminal Domain-Derived Epitopes

2006 ◽  
Vol 80 (16) ◽  
pp. 8263-8266 ◽  
Author(s):  
C. W. Tsang ◽  
X. Lin ◽  
N. H. Gudgeon ◽  
G. S. Taylor ◽  
H. Jia ◽  
...  
Keyword(s):  
T Cell ◽  
Epstein Barr Virus ◽  
T Cell Responses ◽  
Nuclear Antigen ◽  
Target Cells ◽  
Chinese Populations ◽  
Barr Virus ◽  
Cell Responses ◽  
Epstein Barr ◽  
The One

ABSTRACT Epstein-Barr virus nuclear antigen EBNA1, the one viral protein uniformly expressed in nasopharyngeal carcinoma (NPC), represents a prime target for T-cell-based immunotherapy. However, little is known about the EBNA1 epitopes, particularly CD4 epitopes, presented by HLA alleles in Chinese people, the group at highest risk for NPC. We analyzed the CD4+ T-cell responses to EBNA1 in 78 healthy Chinese donors and found marked focusing on a small number of epitopes in the EBNA1 C-terminal region, including a DP5-restricted epitope that was recognized by almost half of the donors tested and elicited responses able to recognize EBNA1-expressing, DP5-positive target cells.

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

scholarly journals Identification of target antigens for the human cytotoxic T cell response to Epstein-Barr virus (EBV): implications for the immune control of EBV-positive malignancies.

1992 ◽  
Vol 176 (1) ◽  
pp. 157-168 ◽  
Author(s):  
R J Murray ◽  
M G Kurilla ◽  
J M Brooks ◽  
W A Thomas ◽  
M Rowe ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Hla Class I ◽  
T Cell Response ◽  
Class I ◽  
Nuclear Antigen ◽  
Cytotoxic T Cell ◽  
Lymphoid Tissues ◽  
Barr Virus ◽  
Viral Antigens ◽  
Epstein Barr

Epstein-Barr virus (EBV), a human herpes virus with oncogenic potential, persists in B lymphoid tissues and is controlled by virus-specific cytotoxic T lymphocyte (CTL) surveillance. On reactivation in vitro, these CTLs recognize EBV-transformed lymphoblastoid cell lines (LCLs) in an HLA class I antigen-restricted fashion, but the viral antigens providing target epitopes for such recognition remain largely undefined. Here we have tested EBV-induced polyclonal CTL preparations from 16 virus-immune donors on appropriate fibroblast targets in which the eight EBV latent proteins normally found in LCLs (Epstein-Barr nuclear antigen [EBNA] 1, 2, 3A, 3B, 3C, leader protein [LP], and latent membrane protein [LMP] 1 and 2) have been expressed individually from recombinant vaccinia virus vectors. Most donors gave multicomponent responses with two or more separate reactivities against different viral antigens. Although precise target antigen choice was clearly influenced by the donor's HLA class I type, a subset of latent proteins, namely EBNA 3A, 3B, and 3C, provided the dominant targets on a range of HLA backgrounds; thus, 15 of 16 donors gave CTL responses that contained reactivities to one or more proteins of this subset. Examples of responses to other latent proteins, namely LMP 2 and EBNA 2, were detected through specific HLA determinants, but we did not observe reactivities to EBNA 1, EBNA LP, or LMP 1. The bulk polyclonal CTL response in one donor, and components of that response in others, did not map to any of the known latent proteins, suggesting that other viral target antigens remain to be identified. This work has important implications for CTL control over EBV-positive malignancies where virus gene expression is often limited to specific subsets of latent proteins.

scholarly journals Robust In Vivo Transduction of a Genetically Stable Epstein-Barr Virus Episome to Hepatocytes in Mice by a Hybrid Viral Vector

2009 ◽  
Vol 83 (7) ◽  
pp. 3249-3257 ◽  
Author(s):  
Sean D. Gallaher ◽  
Jose S. Gil ◽  
Oliver Dorigo ◽  
Arnold J. Berk
Keyword(s):  
Epstein Barr Virus ◽  
Viral Vector ◽  
Hybrid Approach ◽  
Nuclear Antigen ◽  
Transduction Efficiency ◽  
Target Cells ◽  
Delivery Vehicle ◽  
Barr Virus ◽  
Epstein Barr

ABSTRACT To make a safe, long-lasting gene delivery vehicle, we developed a hybrid vector that leverages the relative strengths of adenovirus and Epstein-Barr virus (EBV). A fully gene-deleted helper-dependent adenovirus (HDAd) is used as the delivery vehicle for its scalability and high transduction efficiency. Upon delivery, a portion of the HDAd vector is recombined to form a circular plasmid. This episome includes two elements from EBV: an EBV nuclear antigen 1 (EBNA1) expression cassette and an EBNA1 binding region. Along with a human replication origin, these elements provide considerable genetic stability to the episome in replicating cells while avoiding insertional mutagenesis. Here, we demonstrate that this hybrid approach is highly efficient at delivering EBV episomes to target cells in vivo. We achieved nearly 100% transduction of hepatocytes after a single intravenous injection in mice. This is a substantial improvement over the transduction efficiency of previously available physical and viral methods. Bioluminescent imaging of vector-transduced mice demonstrated that luciferase transgene expression from the hybrid was robust and compared well to a traditional HDAd vector. Quantitative PCR analysis confirmed that the EBV episome was stable at approximately 30 copies per cell for up to 50 weeks and that it remained circular and extrachromosomal. Approaches for adapting the HDAd-EBV hybrid to a variety of disease targets and the potential benefits of this approach are discussed.

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.

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