Human lymphoblastoid cell lines and Epstein-Barr virus: a review of their interrelationships and their relevance to the etiology of leukoproliferative states in man.

The Epstein-Barr virus (EBV), is a herpes-like virus found in continuous cultures of human leukocytic cells derived from certain tumors, from bone marrow and peripheral blood leukocytes of patients with diseases such as leukemia and infectious mononucleosis, and from the blood leukocytes of some normal persons. EBV was discovered in lymphoid cell cultures originating from Burkitt's lymphoma (BL); because it was the first virus to show a regular association with a human malignant tumor, it has received a great deal of attention from experimental oncologists, virologists, epidemiologists, and clinicians in the six years since its discovery. The hypothesis that viruses are a cause of human malignant disease has been explored with increasing energy since studies in lower animals have demonstrated the oncogenic potential of these agents. The RNA tumor viruses of chickens,' mice,2 and cats' have been considered likely models for human leukemia and lymphoma because of the similarity of the diseases in lower animals and in man, and because these agents produce tumors in the species in which they are found in nature. Polyoma and simian virus 40 (SV40), small DNA viruses of the papova group, do not usually produce tumors in their natural host but they are important tools in experimental viral cancerigenesis, because they offer the promise of close genetic and biochemical analysis of malignant transformation in vitro. Some types of human adenoviruses, larger DNA viruses, cause tumors in experimental animals and produce malignant transformation of animal cells in vitro.' Since some adenovirus types are oncogenic and others are not, a great deal of research has been directed toward understanding these differences which, at present, are not fully explained at a molecular level. More recently a fourth group of animal viruses, the herpes group, which are still larger, more complex enveloped viruses with double-stranded DNA, have been regularly associated with tumors both in lower animals and in man. The herpes virus of the Lucke frog renal adenocarcinoma was dis-