scholarly journals 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’

2004 ◽  
Vol 85 (7) ◽  
pp. 2023-2034 ◽  
Author(s):  
Jung-Chung Lin ◽  
Jaw-Ming Cherng ◽  
Hsiung-Ju Lin ◽  
Chi-Wai Tsang ◽  
Yi-Xi Liu ◽  
...  

Full-length sequences of the Epstein–Barr virus (EBV) gene for latent membrane protein (LMP)-1 from 22 nasopharyngeal carcinoma (NPC) biopsy specimens and 18 non-neoplastic counterparts (NPI) were determined. Relative to the B95-8 strain, the amino acid sequences of the toxic-signal and transformation domains were changed variably in NPC and NPI specimens; in contrast, no change was observed in the NF-κB (nuclear factor κB) activation domain. HLA typing revealed that 47 % of NPC and 31 % of NPI specimens were HLA A2-positive. A major A2-restricted epitope within LMP-1 (residues 125–133) was analysed. At residue 126, a change of L→F was detected in 91 % (20/22) of NPC and 67 % (12/18) of NPI specimens. In addition, a deletion at residue 126 was detected in one NPC sample from Taiwan. At residue 129, a change of M→I was observed in all samples, regardless of whether they were NPC or NPI. The changes in this peptide between NPC and NPI specimens, including mutation and deletion, are statistically significant (P<0·05). A recent report indicated that this variant sequence is recognized poorly by epitope-specific T cells. Genotyping results indicated that 96 % of NPC and 67 % of NPI samples carried a type A virus. By scanning the entire sequence of LMP-1, eight distinct patterns were identified. Detailed examination of these patterns revealed that type A strains are more prevalent in NPC than in NPI specimens and are marked by the loss of an XhoI site, the presence of a 30 bp deletion and the presence of a mutated, A2-restricted, T cell target epitope sequence. These results suggest that an EBV strain carrying an HLA A2-restricted ‘epitope-loss variant’ of LMP-1 is prevalent in NPC in southern China and Taiwan.

Author(s):  
Yongguang Tao ◽  
Ying Shi ◽  
Jiantao Jia ◽  
Yiqun Jiang ◽  
Lifang Yang ◽  
...  

Epstein–Barr virus (EBV) was first discovered 50 years ago as an oncogenic gamma-1 herpesvirus and infects more than 90% of the worldwide adult population. Nasopharyngeal carcinoma (NPC) poses a serious health problem in southern China and is one of the most common cancers among the Chinese. There is now strong evidence supporting a role for EBV in the pathogenesis of NPC. Latent membrane protein 1 (LMP1), a primary oncoprotein encoded by EBV, alters several functional and oncogenic properties, including transformation, cell death and survival in epithelial cells in NPC. LMP1 may increase protein modification, such as phosphorylation, and initiate aberrant signalling via derailed activation of host adaptor molecules and transcription factors. Here, we summarise the novel features of different domains of LMP1 and several new LMP1-mediated signalling pathways in NPC. When then focus on the potential roles of LMP1 in cancer stem cells, metabolism reprogramming, epigenetic modifications and therapy strategies in NPC.


2018 ◽  
Vol 109 (2) ◽  
pp. 272-278 ◽  
Author(s):  
Tomokazu Yoshizaki ◽  
Satoru Kondo ◽  
Kazuhira Endo ◽  
Yosuke Nakanishi ◽  
Mitsuharu Aga ◽  
...  

2013 ◽  
Vol 21 (2) ◽  
pp. 256-259 ◽  
Author(s):  
Viviana P. Lutzky ◽  
Pauline Crooks ◽  
Leanne Morrison ◽  
Natasha Stevens ◽  
Joanne E. Davis ◽  
...  

ABSTRACTEpstein-Barr virus (EBV) is associated with nasopharyngeal carcinoma (NPC). We assess the safety and tolerability of adoptive transfer of autologous cytotoxic T lymphocytes (CTLs) specific for the EBV latent membrane protein (LMP) in a patient with recurrent NPC. After infusion, the majority of pulmonary lesions were no longer evident, although the primary tumor did not regress.


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