Integrated and episomal forms of Epstein-Barr virus (EBV) in EBV associated disease.

Epstein-Barr virus (EBV) is known to be linear in viral particles but EBV circularizes into an episomal form after infection. Recently, the presence of integrated EBV DNA has been reported. We investigated EBV integration into the human genome in EBV-associated disease using Southern blotting. One hundred four cases in which the presence of EBV was confirmed by Southern blotting with EBV-W probes were thus analyzed with left- and right-hand end probes of linear EBV. Integrated EBV was demonstrated in 11 of 104 cases; five of 14 cases with B cell lymphoma (36%), one of 12 cases with nasopharyngeal carcinomas (8%), four of 31 cases with natural killer (NK) leukemia/lymphoma (13%) and one of 11 cases with chronic EBV infection (9%). However, none of the 24 T cell lymphoma, seven Hodgkin's disease, or five acute EBV infection cases showed integrated EBV. In addition, seven of the 11 cases with EBV integration (five B cell lymphoma and two NK leukemia/lymphoma) showed only an integration form, however, the other four (two NK leukemia/lymphoma, one nasopharyngeal carcinoma and one chronic EBV infection) showed both integrated and episomal forms. The integrated form was frequently found in B cell lymphoma and especially in high grade B cell lymphoma. Fluorescence in situ hybridization (FISH) was performed in two cases (NK and B cell lymphoma), which represented integrated EBV in Southern blotting and the integration form was confirmed in both. However, it is still uncertain as to whether or not the EBV integration site is directly associated with chromosomal abnormality.