Amino acid changes in functional domains of latent membrane protein 1 of Epstein–Barr virus in nasopharyngeal carcinoma of southern China and Taiwan: prevalence of an HLA A2-restricted ‘epitope-loss variant’

Lin, Jung-Chung; Cherng, Jaw-Ming; Lin, Hsiung-Ju; Tsang, C. W.; Liu, Yixi; Lee, Steven P.

doi:10.1099/vir.0.19696-0

Cited by 31 publications

(42 citation statements)

References 44 publications

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“…Furthermore, we also investigated genomic regions highly linked to the 101 SNPs and found that some are related to the etiology of diseases such as nasopharyngeal carcinoma, which is highly prevalent in Asian populations. Its prevalence in the southern Han is 25 times higher than that in Caucasians [30]. Using Taiwanese patients, the susceptibility locus has been previously mapped to an HLA-A-containing segment between microsatellite markers D6S211 and D6S510 within a 132 kb segment [31].…”

Section: Resultsmentioning

confidence: 99%

A comparison of major histocompatibility complex SNPs in Han Chinese residing in Taiwan and Caucasians

Yang

Lin²,

Hsu

et al. 2006

J Biomed Sci

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SummaryGenetic dissection of complex diseases is both important and challenging. The human major histocompatibility complex is involved in many human diseases and genetic mechanisms. This highly polymorphic chromosome region has been extensively studied in Caucasians but not as well in Asians. Thus, we compared genotypic distributions, linkage disequilibria and haplotype blocks between Caucasian and TaiwanÕs Han Chinese populations. Moreover, we investigated the population admixture and phylogenetic system in Han Chinese residing in Taiwan. The results show that TaiwanÕs Han Chinese differ drastically in genotypic information compared with Caucasians but are relatively homogeneous among the three major ethnic subgroups, Minnan, Hakka and Mainlanders. Differences in allele frequency (AF) between Taiwanese and Caucasians in some disease-associated loci may reveal clues to differences in disease prevalence. The results of ethnic heterogeneity imply that public databases should be used with caution in cases where the study population(s) differs from the population characterized in the database. The high homogeneity we observed among the Taiwanese subpopulations mitigates the possibility of spurious association caused by ignoring population stratification in Taiwanese disease gene association studies. These results are useful for understanding our genetic background and designing future disease gene mapping studies.

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Section: Resultsmentioning

confidence: 99%

A comparison of major histocompatibility complex SNPs in Han Chinese residing in Taiwan and Caucasians

Yang

Lin²,

Hsu

et al. 2006

J Biomed Sci

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“…The EBV oncogene LMP-1 is believed to play a critical role in the cell transformation process that leads to malignancy, especially in nasopharyngeal carcinoma (25). The discovery that lyLMP-1 down-regulates LMP-1 oncogenic activity in epithelial cells is especially interesting in light of recent studies suggesting strong negative selection pressure in nasopharyngeal carcinoma against EBV strains encoding the lyLMP-1 ORF (6,14,19).…”

Section: Discussionmentioning

confidence: 99%

“…However, the presence or absence of the lyLMP-1 open reading frame (ORF) is determined by the sequence at LMP-1 gene codon number 129 in the third exon: ATG (methionine) serves as the lyLMP-1 initiator, whereas ATT (isoleucine) prohibits translation of lyLMP-1 from the ED-L1A transcript (6). Molecular epidemiologic studies demonstrate that the lyLMP-1 ORF is present in 60% of EBV strains that circulate in nature (6) but consistently absent from the LMP-1 genes found in nasopharyngeal carcinoma (6,14,19), despite apparent transcriptional activity of the ED-L1A promoter in nasopharyngeal carcinoma (20). These observations suggest that selective pressures act in favor of LMP-1 expression, but against lyLMP-1 expression, in the pathogenesis of nasopharyngeal carcinoma.…”

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confidence: 99%

Oncogenic Activity of Epstein-Barr Virus Latent Membrane Protein 1 (LMP-1) Is Down-Regulated by Lytic LMP-1

Pandya¹,

Walling

2006

J Virol

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The Epstein-Barr virus (EBV) is an oncogenic human herpesvirus. EBV latent membrane protein 1 (LMP-1) is a viral oncogene that manifests its oncogenic phenotype through activation of cellular signaling pathways involved in cell growth, survival, differentiation, and transformation. Lytic LMP-1 (lyLMP-1) is a related EBV gene without oncogenic properties. The lyLMP-1 gene is found in 60% of the EBV strains circulating in nature, but it is not found in EBV strains associated with nasopharyngeal carcinoma. We recently demonstrated that lyLMP-1 down-regulates the half-life of LMP-1 in epithelial cells. Therefore in this study, we tested the hypothesis that lyLMP-1 concomitantly down-regulates LMP-1 oncogenic activity. The results demonstrated that lyLMP-1 inhibits LMP-1-mediated intracellular signaling activation, epithelial cell growth and survival, and fibroblast cell transformation in a dose-dependent manner. Lytic LMP-1 manifested this effect through the promotion of LMP-1 degradation and a reduction in the expressed quantity of LMP-1. Thus, lyLMP-1 functions as a posttranslational negative regulator of LMP-1 oncogenesis. These results support a model of EBV-associated epithelial oncogenesis in which lyLMP-1 may act in vivo to reduce the risk of LMP-1-mediated transformation and is therefore subjected to negative selection in nasopharyngeal carcinoma pathogenesis. Epstein-Barr virus (EBV)is an oncogenic human herpesvirus associated with a broad spectrum of benign and malignant diseases, including infectious mononucleosis, oral hairy leukoplakia, African Burkitt's lymphoma, Hodgkin's disease lymphoma, lymphoproliferative disorders of immunocompromised hosts, and nasopharyngeal carcinoma. The EBV latent membrane protein 1 (LMP-1) is a viral oncogene (30) that is believed to be important in the pathogenesis of many EBVassociated diseases, including nasopharyngeal carcinoma (25). In the B958 EBV strain, LMP-1 is a 63-kDa protein of 386 amino acids encoded by the BNLF1 gene. LMP-1 localizes to cellular membranes and functions as a constitutively active tumor necrosis factor receptor homologue that propagates intracellular signaling, including the NF-B, cJun N-terminal protein kinase/AP-1, and Janus kinase/STAT pathways (5,12,15,27). Through these signaling pathways, LMP-1 generates a myriad of effects on host cell growth, differentiation, and apoptosis, including growth promotion and survival in epithelial cells (4,11,16,23,32) and transformation of rodent fibroblasts (3, 30). Although the mechanisms by which LMP-1 influences cell biology have been intensively studied, little is known about the mechanisms that regulate LMP-1 oncogenic activity. Some EBV strains also encode an amino-terminally truncated form of LMP-1 called lytic LMP-1 (lyLMP-1). Transcription of lyLMP-1 is driven by the ED-L1A promoter that is located in the first intron of the LMP-1 gene and that is present in all EBV strains (6, 17, 29) (Fig. 1). However, the presence or absence of the lyLMP-1 open reading frame (ORF) is determined by the sequence ...

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“…The stereo chemical quality of predicted of LMP-1 structure was analyzed through residue by residue geometry and all geometry of protein structure using RAMPAGE server [16]. Ramachandran plots were drawn for this protein structure.…”

Section: Resultsmentioning

confidence: 99%

“…LMP-1 is easy to interact with nicotine and nitrosamine but the binding is weak and not stable. Latent membrane protein 1 (LMP-1) is of special interest since it is generally considered to be the main EBV oncogene 16 . EBV, in conjunction with environmental and genetic factors, plays a role in the development of NPC 17 .…”

Section: Discussionmentioning

confidence: 99%

LMP-1 ve Nazofaringial Karsinoma

Budiningrum¹,

Rofi\\\i²,

Suharjono³

et al. 2014

Cukurova Medical Journal

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Purpose: This study aims to determine the interaction of LMP-1 with H2O2 , nitrosamine, and nicotine to predict the external factor that affected LMP-1, which activates lytic phase on nasopharyngeal carcinoma (NPC). Materials and Methods:The amino acid sequence of human LMP1 (GI: 343177335) and compound structure of H2O2 (ID:784), nicotine (ID: 89594), and nitrosamine (ID: 37183) was obtained from database The National center of Biotechnology Information. The 3-dimension modeling structure of LMP-1 predicted using SWISS-MODEL web server. Hex 6.12 was used for the purpose of docking of the lead with the target molecule. Ligand details interaction then detected by LigPlus+ v.1.4.4 software. Molecular graphics and analysis were performed with PyMOL. Results: LMP-1 has interaction with H2O2 , nitrosamine, and nicotine. Total energy that use of LMP-1 to interaction with H2O2 (-67,79 kJ/mol) is lowest than interaction with nicotine (-149,43 kJ/mol) and nitrosamine (-82,93 kJ/mol). The kind of interaction between LMP-1 and H2O2 is hydrogen bond whereas interaction of LMP-1 between nicotine and nitrosamine are hydrophobic bond. Conclusions:LMP-1 has strongest interaction with H2O2 than nicotine and nitrosamine. This is predicted that H2O2 is external factor that affect LMP-1 switching to lytic infection in NPC patients. Keywords: H2O2 , LMP-1; nasopharyngeal carcinoma, nicotine, nitrosamine

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Amino acid changes in functional domains of latent membrane protein 1 of Epstein–Barr virus in nasopharyngeal carcinoma of southern China and Taiwan: prevalence of an HLA A2-restricted ‘epitope-loss variant’

Cited by 31 publications

References 44 publications

A comparison of major histocompatibility complex SNPs in Han Chinese residing in Taiwan and Caucasians

A comparison of major histocompatibility complex SNPs in Han Chinese residing in Taiwan and Caucasians

Oncogenic Activity of Epstein-Barr Virus Latent Membrane Protein 1 (LMP-1) Is Down-Regulated by Lytic LMP-1

LMP-1 ve Nazofaringial Karsinoma

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