Epstein-Barr virus strain variation in nasopharyngeal carcinoma from the endemic and non-endemic regions of China.
Nasopharyngeal carcinoma (NPC) occurs with a striking geographic incidence and is endemic in parts of southern China, where it is the major cause of cancer death. Epstein-Barr virus (EBV) is detected in all cells of the majority of NPC cases regardless of geographic origin. A small subset of EBV genes is expressed in NPC, including the latent membrane protein (LMP-1). LMP-1 is essential for transformation of B lymphocytes and is considered to be the EBV oncogene. This analysis of the DNA sequence variation within the LMP-1 gene reveals a consensus sequence for a strain, denoted China1, which predominates in East Asia where NPC is endemic. The China1 strain is characterized by nucleotide changes at 13 loci in the amino terminal portion of the LMP-1 gene when compared with the B95-8 prototype, including a point mutation resulting in the loss of an Xho1 restriction site. This strain was present in 9 of 15 NPC biopsy specimens from the endemic region and in 7 of 13 from northern China, where NPC is non-endemic. A second strain, China2, was detected in 4 of 15 endemic isolates and in 2 of 13 non-endemic isolates; this strain was characterized by a cluster of 5 nucleotide changes in the amino terminal portion of LMP-1 in addition to those seen in China1. It was also marked by distinct changes in the carboxy terminal region of LMP-1 including the retention of amino acids 343-352. All China1 isolates were EBV type 1, whereas the China2 isolates did not correlate with EBV type. Phylogenetic relationships between these 2 strains were determined, as were signature amino acid alterations that discriminate between them.
Sung
N S
NS
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill 27599, USA.
Edwards
R H
RH
Seillier-Moiseiwitsch
F
F
Perkins
A G
AG
Zeng
Y
Y
Raab-Traub
N
N
D001483:Base Sequence; D002681:China / Q000453:epidemiology; D016384:Consensus Sequence; D004279:DNA, Viral / Q000235:genetics; D019353:Endemic Diseases; D005814:Genes, Viral; D014644:Genetic Variation; D006566:Herpesviridae Infections / Q000453:epidemiology* / Q000821:virology*; D004854:Herpesvirus 4, Human / Q000145:classification* / Q000235:genetics*; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000453:epidemiology* / Q000821:virology*; D010802:Phylogeny; D012689:Sequence Homology, Nucleic Acid; D014412:Tumor Virus Infections / Q000453:epidemiology* / Q000821:virology*; D014763:Viral Matrix Proteins / Q000032:analysis / Q000235:genetics
D004279:DNA, Viral; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins