Epstein-Barr virus genomes in lymphoid cells: activation in mitosis and chromosomal location

Biotin-labeled Epstein-Barr virus (EBV)-specific DNA probes have been used to detect viral genomes by in situ hybridization. Immunocytochemically amplified signals produced by the hybridized probe allow visualization of viral DNA even in cells previously reported to contain only one or two EBV genomes. In EBV producer lymphoid cell lines, such as B95-8, P3HR-1, or Daudi, activation of latent EBV DNA could be observed in mitotic cells; in non-virus-producing cells of these same lines, EBV was found to be present in low copy numbers. Noninducible cell lines such as IB4, AW-Ramos, and Namalwa exhibited low but clearly positive hybridization. Unexpectedly, significant variations in the amounts of EBV DNA per cell were observed between individual cells of these lines. The EBV DNA in the cloned IB4 cell line was localized to chromosome 4 in metaphase cells, but in the noncloned converted line AW-Ramos, the location of integrated viral DNA was essentially random.