Specific latent membrane protein 1 gene sequences in type 1 and type 2 Epstein-Barr virus from nasopharyngeal carcinoma in Hong Kong

Abstract

We reported previously that a characteristic Epstein‐Barr virus latent membrane protein 1 (EBV‐LMP1) gene was associated with nasopharyngeal carcinoma (NPC) in Hong Kong. It showed a 30 bp deletion at the carboxyl terminus with specific amino acid substitution Asp at codon 335 with reference to Gly in B95‐8 LMP1. This deletion variant Asp335 was present in over 90% of NPC biopsy specimens. The present study attempted to determine the whole encoding sequence of the LMP1 gene in different EBV isolates from NPC, and its relation with EBV types. We found that 92% (34/37) of primary NPC tumours harboured EBV‐1 and possessed the LMP1 deletion variant, of which 86% were Asp335 and 6% were Gly335. EBV‐2 was present in 8% (3/37) of tumours and all contained the retention variant of the LMP1 gene. Sequencing of the whole encoding region of the LMP1 gene revealed that the deletion variant Asp335 and deletion variant Gly335 carried similar sequences. They showed 43 common nucleotide substitutions in 41 codons with reference to B95‐8. The retention variant showed 52 base changes in 46 codons compared with B95‐8. The amino acid alterations in both the deletion and retention variants were mostly clustered at the transmembrane domain of the protein. Furthermore, half of the substitutions were common to both variants, suggesting a common evolutionary selection pressure. Nonetheless, the 2 LMP1 variants showed differences in nucleotide alterations and were associated with different EBV types, suggesting the presence of 2 distinct EBV strains in Hong Kong NPC. Int. J. Cancer 76:399–406, 1998.© 1998 Wiley‐Liss, Inc.

Genomic Diversity of Epstein-Barr Virus Genomes Isolated from Primary Nasopharyngeal Carcinoma Biopsy Samples

“…To investigate the role of EBV genomic variation in the pathogenesis of NPC, EBV strains had been characterized in NPC by genotyping polymorphic markers in the EBER1 and -2, LMP1, BHRF1, BZLF1, and EBNA1 gene loci in tumor samples obtained from China, southern Asia, and northern Africa (2-7). Association of LMP1 deletion variant Asp335 with NPC in Hong Kong was reported (8). Specific EBNA1 (V-val) and LMP1 subtypes (China 1) also showed preferential occurrence in NPC biopsy specimens (9,10).…”

The C-terminal Activating Region 2 of the Epstein-Barr Virus-encoded Latent Membrane Protein 1 Activates NF-κB through TRAF6 and TAK1

“…Well as the Prototypic LMP1 Does-Many different LMP1 variants have been found over the years (36). One of them, LMP1(D335), was frequently found in biopsies from NPC patients in Hong Kong (36).…”

Latent membrane protein 1 suppresses RASSF1A expression, disrupts microtubule structures and induces chromosomal aberrations in human epithelial cells

“…As the transfection efficiency of the immortalized NP69 cells is low, HeLa, HaCaT and SCC1F cells were chosen as recipient cells because of their higher rates of transient transfection (50-80%). The prevalent 2117-LMP1 variant isolated from NPC patients in Hong Kong (Cheung et al, 1998) was used in this part of the study. The functional properties of this LMP1 variant have been previously characterized (Lo et al, 2003(Lo et al, , 2004a.…”

“…Sources and references of the expression plasmids used are: prevalent LMP1 suppresses RASSF1A expression C Man et al LMP1 variant of NPC (2117-LMP1) isolated from an NPC xenograft (Cheung et al, 1998); prototype LMP1 (B95.8-LMP1) was cloned from the B95.8 cell line. The prevalent variant was cloned into the pcDNA3.1 expression vector (Invitrogen, CA, USA).…”