Characterization of the Serological Response in Man to the Latent Membrane Protein and the Six Nuclear Antigens Encoded by Epstein-Barr Virus

Rowe, Martin; Finke, Jürgen; Szigeti, Robert; Klein, George

doi:10.1099/0022-1317-69-6-1217

Cited by 45 publications

(49 citation statements)

References 33 publications

(29 reference statements)

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“…Antibodies to latent infection proteins such as EBNA1, EBNA2 and LMP have also been found in sera from NPC patients, but they can also be present in sera from patients with other EBVrelated disorders (Foong et al, 1990;Seigneurin et al, 1987;Rowe et al, 1988). In this paper we describe the first case of a latent infection protein with an antibody response restricted to NPC patients.…”

Section: Discussionmentioning

confidence: 85%

Characterization of the Antibody Response to the Latent Infection Terminal Proteins of Epstein-Barr Virus in Patients with Nasopharyngeal Carcinoma

Frech

Zimber-Strobl²,

Yip

et al. 1993

Journal of General Virology

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Human sera were tested for antibodies against the Epstein-Barr virus (EBV) latent infection terminal proteins (TPs). Anti-TP IgG and IgA antibodies were detected by an indirect immunofluorescence assay of insect cells expressing a recombinant TP1. Out of 301 human sera of patients with EBV-related and EBVunrelated disorders, only sera from patients with nasopharyngeal carcinoma (NPC) (32/83; 38 %) showed anti-TP antibodies. Studies on serial sera from German and Hong Kong NPC patients revealed a decline of anti-TP antibodies during tumour therapy, and none of these antibodies were identified in patients with early tumour stages or in remission. Comparative studies of TP1-specific polyclonal rabbit antisera and human TPpositive sera showed clear differences in the TP epitopes recognized by each. Human antisera contained antibodies only to native epitopes in exons 2 to 7 of TP1 whereas rabbit antisera reacted only with epitopes located in the first exon and, additionally, exhibited EBV strain specificities.

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Section: Discussionmentioning

confidence: 85%

Characterization of the Antibody Response to the Latent Infection Terminal Proteins of Epstein-Barr Virus in Patients with Nasopharyngeal Carcinoma

Frech

Zimber-Strobl²,

Yip

et al. 1993

Journal of General Virology

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“…As with previous studies (22,(30)(31)(32)(33)(34)(35)(36), an MHC class II peptide binding predictive algorithm (29) was used to select candidate peptides from the LMP1 sequence that would bind to the products of three common human MHC class II alleles (HLA-DR1, HLA-DR4, and HLA-DR7). Three peptides, LMP1 [35][36][37][38][39][40][41][42][43][44][45][46][47][48][49] (ALLFWLYIVMSDWTG), LMP1 102-116 (GQALFLGIVLFIFGC), and LMP1 159-175 (YLQQNWWT-LLVDLLWLL) were identified as potentially binding the three MHC class II alleles (data not presented), suggesting these could function as promiscuous HTL epitopes. In past studies, we have observed that peptide sequences predicted to bind to HLA-DR1, HLA-DR4, and HLA-DR7 have elicited HTL responses restricted by additional MHC class II alleles, such as DR9, DR13, DR15, or DR53 (22,30,32,(34)(35)(36).…”

Section: Resultsmentioning

confidence: 99%

Induction of EBV–Latent Membrane Protein 1–Specific MHC Class II–Restricted T-Cell Responses against Natural Killer Lymphoma Cells

Kobayashi¹,

Nagato

Takahara

et al. 2008

Cancer Research

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EBV-encoded latent membrane protein 1 (LMP1) has oncogenic potential and is expressed in many EBV-associated malignancies. Although LMP1 is regarded as a potential tumor-associated antigen for immunotherapy and several LMP1-specific MHC class I-restricted CTL epitopes have been reported, little is known regarding MHC class II-restricted CD4 helper T-lymphocyte (HTL) epitopes for LMP1. The goal of the present studies was to determine whether MHC class IIrestricted CD4 T-cell responses could be induced against the LMP1 antigen and to evaluate the antitumor effect of these responses. We have combined the use of a predictive MHC class II binding peptide algorithm with in vitro vaccination of CD4 T cells using candidate peptides to identify naturally processed epitopes derived from LMP1 that elicit immune responses against EBV-expressing tumor cells. Peptide LMP1 [159][160][161][162][163][164][165][166][167][168][169][170][171][172][173][174][175] was effective in inducing HTL responses that were restricted by HLA-DR9, HLA-DR53, or HLA-DR15, indicating that this peptide behaves as a promiscuous T-cell epitope. Moreover, LMP1 159-175 -reactive HTL clones directly recognized EBV lymphoblastoid B cells, EBV-infected natural killer (NK)/T-lymphoma cells and naturally processed antigen in the form of LMP1+ tumor cell lysates presented by autologous dendritic cells. Because the newly identified epitope LMP1 159-175 overlaps with an HLA-A2-restricted CTL epitope (LMP1 [159][160][161][162][163][164][165][166][167] ), this peptide might have the ability to induce simultaneous CTL and HTL responses against LMP1. Overall, our data should be relevant for the design and optimization of T-cell epitope-based immunotherapy against various EBVassociated malignancies, including NK/T cell lymphomas. [Cancer Res 2008;68(3):901-8]

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“…Although the sensitivity of existing assays has been reported, [36][37][38][39][40][41] few studies have been conducted for the purpose of screening high-risk populations and determining whether their high sensitivities in diagnosis are consistent in screening conditions. Current use of EBV viral capsid antigen (VCA) immunoglobulin A (IgA) for screening in familial NPC yields 83% sensitivity and 87% specificity.…”

Section: Discussionmentioning

confidence: 99%

Profiling of Epstein‐Barr virus‐encoded microRNAs in nasopharyngeal carcinoma reveals potential biomarkers and oncomirs

Wong

Kong

Tsang

et al. 2011

Cancer

142

133

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BACKGROUND: Epstein-Barr virus (EBV) microRNAs are abundant in nasopharyngeal carcinoma (NPC) tumors. With recent advances in serum microRNA detection, the distinct presence of EBV microRNAs in serum could aid in screening endemic regions for NPC. A proposed network of genes targeted by these microRNAs could also shed light on EBV-associated tumorigenesis. METHODS: MicroRNA microarray profiling of 5 paired NPC biopsies was followed by validation of 12 up-regulated EBV microRNAs (BART1-3p, 2-5p, 5, 6-5p, 6-3p, 7, 8, 9, 14, 17-5p, 18-5p, 19-3p) in 15 additional cases by real-time polymerase chain reaction. Tumor (cellular) and serum microRNA copy numbers from the same 15 patients were correlated. Expression of the same microRNAs were also examined in EBV-positive cell lines C666 and NP460hTERTþEBV. Bioinformatic tools helped predict cellular target genes, which were later confirmed by gene expression analysis. RESULTS: The authors' high-throughput approach shows that EBV microRNAs are generally more up-regulated than microRNAs of human origin. Twenty-nine of 39 EBV microRNAs were significantly up-regulated in tumor versus their nontumor biopsies (P < .05). Upon successfully validating 12 selected EBV microRNAs in 15 additional paired NPC cases, the authors found that their distinct presence in the serum of NPC patients positively correlated with cellular copy numbers of EBV microRNAs. Further investigation of potential EBV microRNA target genes revealed inhibition of tumor suppressor genes (eg, PTEN) and extensive deregulation of several pathways frequently involved in NPC (eg, Wnt signaling). CONCLUSIONS: Increasing knowledge of host-virus interaction via microRNAs may provide feasible explanations underlying NPC tumorigenesis along with the development of biomarkers for screening high-risk populations. Cancer 2012;118:698-

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Characterization of the Serological Response in Man to the Latent Membrane Protein and the Six Nuclear Antigens Encoded by Epstein-Barr Virus

Cited by 45 publications

References 33 publications

Characterization of the Antibody Response to the Latent Infection Terminal Proteins of Epstein-Barr Virus in Patients with Nasopharyngeal Carcinoma

Characterization of the Antibody Response to the Latent Infection Terminal Proteins of Epstein-Barr Virus in Patients with Nasopharyngeal Carcinoma

Induction of EBV–Latent Membrane Protein 1–Specific MHC Class II–Restricted T-Cell Responses against Natural Killer Lymphoma Cells

Profiling of Epstein‐Barr virus‐encoded microRNAs in nasopharyngeal carcinoma reveals potential biomarkers and oncomirs

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