Recently established Epstein‐Barr virus (EBV)‐positive Burkitt's lymphoma (BL) cell lines, carrying chromosomal translocations indicative of their malignant origin, have been monitored for their degree of in vitro progression towards a more ‘lymphoblastoid’ cell surface phenotype and growth pattern, and for their expression of three EBV latent gene products which are constitutively present in all virus‐transformed normal lymphoblastoid cell lines (LCLs). BL cell lines which stably retained the original tumour biopsy phenotype on serial passage were all positive for the nuclear antigen EBNA 1 but did not express detectable amounts of two other ‘transforming’ proteins, EBNA 2 and the latent membrane protein (LMP). This novel pattern of EBV gene expression was also observed on direct analysis of BL biopsy tissue. All three viral proteins became detectable, however, in BL cell lines which had progressed towards a more LCL‐like phenotype in vitro. This work establishes a link between B cell phenotype and the accompanying pattern of EBV latent gene expression, and identifies a novel type of EBV:cell interaction which may be unique to BL cells.
Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus associated with the development of both lymphoid and epithelial tumours. As a common virus infection, EBV appears to have evolved to exploit the process of B cell development to persist as a life-long asymptomatic infection. However, the virus can contribute to oncogenesis as evidenced by its frequent detection in certain tumours, namely Burkitt's lymphoma (BL), post-transplant B cell lymphomas, Hodgkin's disease (HD) and nasopharyngeal carcinoma (NPC), and by its unique ability to efficiently transform resting B cells in vitro into permanently growing lymphoblastoid cell lines (LCLs). These transforming effects are associated with the restricted expression of EBV genes such that only a subset of so-called latent virus proteins are expressed in virus infected tumours and in LCLs. Distinct forms of EBV latency are manifest in the different tumours and these appear to be a vestige of the pattern of latent gene expression used by the virus during the establishment of persistent infection within the B cell pool. This review summarises our current knowledge of EBV latent gene function and how this relates to the role of the virus in the aetiology of different tumours.
Epstein-Barr virus (EBV) has been associated with serious or fatal lymphoproliferative disease in immunocompromised patients. EBV nuclear protein 2 and latent membrane protein are characteristically expressed in B lymphocytes proliferating in vitro in response to growth transformation by EBV. These two proteins are thought to be effectors of lymphocyte growth since they increase the expression of B-lymphocyte activation (CD23) and cell-adhesion (LFA 3 and ICAM 1) molecules in vitro. Using monoclonal antibody-immune microscopy, we have demonstrated that these two EBV proteins and their associated B-lymphocyte activation or adhesion molecules are expressed in the infiltrating B lymphocytes in immunocompromised patients with EBV lymphoproliferative disease. These monoclonal antibodies should be useful in the early diagnosis of EBV lymphoproliferative disease and in distinguishing it from other B-lymphocyte cancers associated with EBV, such as Burkitt's lymphoma. The finding of EBV nuclear protein 2 and latent membrane protein and their associated activation or adhesion molecules provides a further pathophysiologic link between EBV and the proliferation of B lymphocytes in immunocompromised patients.
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