|Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1996: ¥1,400,000 (Direct Cost: ¥1,400,000)
Epstein-Barr virus (EBV) is implicated in the pathogenesis of a number of human malignancies, including Burkitt's lymphoma, nasopharyngeal carcinoma, Hodgkin's disease, peripheral T-cell lyphome, and gastric carcinoma. In spite of its association with malignancies of various histological lineages, experimental EBV infection has been extremely difficult with B-lymphocytes being the only exception, in which in vitro EBV infection easily establishes persistent infection. In this project, we attempted to establish new experimental systems of persistent EBV infection of non-B-cell lineages, by using recombinant EBV with a positive selection marker. We isolated EBV-infected clones of a human T-cell line MT-2 and characterized their EBV gene expression. The results indicated that they expressed EBV nuclear antigen 1 (EBNA1), latent membrane protein 1 (LMP1), LMP2A, BARF0, and EBER, while EBNA2 was barely detectable. Thus far, the EBV gene expression in MT-2 cells was similar to that in peripheral T-cell lymphoma. However, MT-2 cells expressed also EBNA3 and proteins of the early virus-replicative cycle, including BZLF, and was different with this respect from peripheral T-cell lymphoma. This pattern of EBV gene expression seen in MT-2 cells is clearly different from that seen in human B-cell lines BJAB and Louckes that are persistently infected with similar recombinant EBV.Thus, MT-2 cells may be useful to analyze EBV gene regulation in T-cell lineage.
In our effort to establish experimental system of persistent EBV infection in the epithelial-cell lineage, we attempted to introduce the gene encoding EBV receptor to human epithelial cell lines. However, we still have not achieved its stable and high-level expression, that is required for efficient EBV infection.