The history of Epstein-Barr virus (EBV) research is distinguished by concurrences of precise observation, chance events, and a huge amount of solid research. Denis Burkitt, a dedicated surgeon and visionary in medical science, observed and described with great acuity a lymphoma of children in equatorial Africa that was later named after him (Burkitt, 1958; Burkitt, 1962). In the wake of efforts to identify an infectious agent behind Burkitt lymphoma, tumor cells were grown in culture, and herpesvirus-like particles were discovered in tumor cells by electron microscopy (Epstein et al., 1964; Pulvertaft, 1964). Subsequently, EBV was implicated as the causative agent of infectious mononucleosis (IM), only after a lab technician in the Henle laboratory in Philadelphia experienced an IM and seroconverted in the process (Henle et al., 1968). Also known as human herpesvirus 4, EBV is one of eight known human pathogenic herpesviruses. Based on its tissue tropism and biology and later also on the basis of sequence comparisons, it was classified as belonging to the genus Lymphocryptovirus (LCV) within the subfamily Gammaherpesvirinae of the family Herpesviridae. Herpesviruses are large DNA viruses with a linear double-stranded DNA genome inside a membrane-coated icosaedrical capsid. The EBV genome has a length of 172 kilobase pairs. As the first herpesvirus to be completely sequenced, EBV served as the subject of a trial run toward larger sequencing projects such as the human genome project (Baer et al., 1984). EBV shares its strong tissue tropism for B lymphocytes with other members of the LCV genus of which it is considered prototypical. The virus is associated with a wide variety of neoplasms (Table 8.1; for review see Rickinson and Kieff, 2001; Thompson and Kurzrock, 2004). These include lymphoid tumors like Burkitt lymphoma (BL), Hodgkin's disease (HD), NK/T cell lymphoma, lymphoproliferations in solid organ transplant or bone marrow recipients (post-transplantation lymphoproliferative disease; PTLD), and AIDS-associated lymphomas (Harabuchi et al., 1990; Hamilton-Dutoit et al., 1993; Bellas et al., 1996; Carbone et al., 1998; Chapman and Rickinson, 1998). EBV is also associated with epithelial malignancies, especially with undifferentiated nasopharyngeal carcinoma (NPC), gastric carcinoma, carcinomas of the salivary glands, and rare cases of thymic carcinoma (Shibata and Weiss, 1992; Osato and Imai, 1996). Leiomyosarcoma, a neoplasm of mesothelial origin, is also highly associated with EBV (McClain et al., 1995). The association of EBV with liver and breast carcinoma is disputed and remains to be firmly established (Herrmann and Niedobitek, 2003). Due to its strong association with endemic BL, EBV has been called the Rosetta stone of tumor virology (de The, 1984, 1985). However, because almost the entire adult world population is latently infected with the virus, the challenge is to explain the discrepancy between the extremely high infection rates with EBV and very low overall tumor incidences in molecular terms and on the background of the natural history of primary EBV infection.
ASJC Scopus subject areas
- Immunology and Microbiology(all)