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'.
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-kappaB (nuclear factor kappaB) 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.
Lin
Jung-Chung
JC
Department of Microbiology, Tzu Chi University School of Medicine, 701 Section 3, Chung Yang Road, Hualien 970, Taiwan, ROC.
Cherng
Jaw-Ming
JM
Department of Internal Medicine, Tzu Chi General Hospital, Hualien, Taiwan, ROC.
Lin
Hsiung-Ju
HJ
Department of Pathology, Kaohsiung Medical University, China.
Tsang
Chi-Wai
CW
CRC Institute for Cancer Studies, University of Birmingham, Birmingham, UK.
Liu
Yi-Xi
YX
Department of Virology, Cancer Research Institute, Chinese Academy of Medical Sciences, Beijing, China.
Lee
Steven P
SP
CRC Institute for Cancer Studies, University of Birmingham, Birmingham, UK.
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001483:Base Sequence; D002681:China; D017931:DNA Primers; D000939:Epitopes / Q000235:genetics; D014644:Genetic Variation; D015789:HLA-A2 Antigen / Q000235:genetics*; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D009303:Nasopharyngeal Neoplasms / Q000473:pathology* / Q000821:virology*; D010446:Peptide Fragments / Q000737:chemistry; D016133:Polymerase Chain Reaction; D015183:Restriction Mapping; D013624:Taiwan; D014763:Viral Matrix Proteins / Q000737:chemistry*
D017931:DNA Primers; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D000939:Epitopes; D015789:HLA-A2 Antigen; D016328:NF-kappa B; D010446:Peptide Fragments; D014763:Viral Matrix Proteins