M Heller

Repeat arrays in cellular DNA related to the Epstein-Barr virus IR3 repeat.

We isolated clones and determined the sequence of portions of mouse and human cellular DNA which cross-hybridize strongly with the IR3 repetitive region of Epstein-Barr virus. The sequences were found to be tandem arrays of a simple sequence based on the triplet GGA, very similar to the IR3 repeat. The cellular repeats have distinct differences from the viral repeat region, however, and their sequences do not appear capable of being translated into a purely glycine-plus-alanine protein domain like the portion of the Epstein-Barr nuclear antigen coded by IR3. Although the relationship between IR3 and the cellular repeats is left unclear, the cellular repeats have many interesting features. The tandem arrays are about 1 to several kilobases long, much shorter than satellite tandem repeats and larger than other interspersed, tandem repeats. Each of the repeats is a distinct variation, perhaps diverged from a common sequence, (GGA)n. This family is present in the genomes of all species tested and appears to be a ubiquitous feature of all higher eucaryotic genomes.

Biochemistry of Epstein—Barr Virus

The objective of this introduction is to develop concisely the context in which biochemical studies of Epstein—Barr virus (EBV) have been undertaken. Elements of history and biology are relevant to an understanding of the somewhat unusual course of biochemical research with EBV.

Persistence and Expression of the Epstein-Barr Virus Genome in Latent Infection and Growth Transformation of Lymphocytes

Epstein-Barr Virus (EBV) is believed to be an important etiologic agent of nasopharyngeal cancers (NPC) especially of the anaplastic type since (i) NPC cells invariably harbor EBV (Wolf et al., 1975; Huang et al., 1974; Klein et al., 1974); (ii) EBV is believed to be a cause of human B lymphocyte tumors (Epstein and Achong, 1978); (iii) the immune response to EBV infection is predictive of NPC development and of prognosis (Henle et al., 1970; Zeng et al., 1980; Pearson et al., 1984); and (iv) most NPC tumors originate from an unique anatomic site where there is closest proximity between lymphoid cells in which EBV is latent and epithelial cells in which tumor originates (Prasad 1981). Because of difficulties in infecting epithelial cells with EBV and in propagating NPC cells in vitro, current knowledge of EBV-induced cell proliferation comes mostly from the human B-lymphocyte tumor model. Not only is EBV almost always present in burkitt lymphoma cells (Nonoyama et al., 1973; Lindahl et al., 1974); nut also, virus infection of lymphocytes in vitro leads to cell proliferation (Henle et al., 1976; Pope et al., 1968), virus-infected cells from tumors in nonhuman primates (Miller et al., 1977), and virus-transformed cells of varying stages of oncogenic potential can be grown in continuous culture (Nilsson 1971).