Review

Epstein-Barr virus and gastric carcinoma

K Takada¹

¹ Department of Tumor Virology, Institute for Genetic Medicine, Hokkaido University, N15 W7, Kita-ku, Sapporo 060–8638, Japan

Correspondence to:
Dr Takada kentaka{at}med.hokudai.ac.jp

The Epstein-Barr virus (EBV) is detected in the tissue of about 10% of gastric carcinoma cases throughout the world. In each case, 100% of carcinoma cells are infected with EBV. Analysis of EBV in carcinoma biopsies indicates that carcinoma is formed by the proliferation of a single EBV infected cell. These findings suggest that EBV plays an important role in the development of EBV positive gastric carcinomas. The EBV genes expressed are EBV determined nuclear antigen 1 (EBNA1), two small non-polyadenylated RNAs known as EBER1 and EBER2, and the transcripts from the BamHI-A region (BARF0); in addition, some cases also express a small amount of latent membrane protein 2A (LMP2A). Epithelial cells are refractory to EBV infection in vitro. This has hampered the study of the role of EBV in epithelial malignancies. The use of recombinant EBV carrying a selectable marker has enabled this difficulty to be overcome. EBV infected cell clones can be obtained from most carcinoma cell lines examined, and it was found that cell to cell contact was an efficient mode of EBV infection. Furthermore, it was possible to immortalise primary gastric epithelial cells by EBV infection. The cells expressed identical EBV genes to those typically seen in EBV positive gastric carcinoma, and showed accelerated malignant properties, including growth in soft agarose and tumorigenicity in severe combined immunodeficient (SCID) mice. These results suggest that EBV contributes to the maintenance of the malignant phenotype of EBV positive gastric carcinoma.

Key Words: Epstein-Barr virus • gastric carcinoma • epithelial cell

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