Epstein-Barr virus strain variation in nasopharyngeal carcinoma from the endemic and non-endemic regions of China

Abstract

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- I). LMP-I 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-I gene reveals a consensus sequence for a strain, denoted China I, which predominates in East Asia where NPC is endemic. The China I strain is characterized by nucleotide changes at 13 loci in the amino terminal portion of the LMP-I gene when compared with the B95-8 prototype, including a point mutation resulting in the loss of an Xhol 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 IS endemic isolates and in 2 of 13 nonendemic isolates; this strain was characterized by a cluster of 5 nucleotide changes in the amino terminal portion of LMP- I in addition to those seen in China 1. It was also marked by distinct changes in the carboxy terminal region of LMP-I including the retention of amino acids 343-352. All China 1 isolates were EBV type I, whereas the China 2 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.