EBV DNA in nonlymphoid cells of nasopharyngeal carcinomas and in a malignant lymphoma obtained after inoculation of EBV into cottontop marmosets.

Epstein-Barr viral (EBV) DNA has been regularly demonstrated in biopsy material from two different human tumors: Burkitt's lymphoma and nasopharyngeal carcinoma (zur Hausen et al. 1970, 1974b; Nonoyama and Pagano 1973; Wolf et al. 1973). Patients carrying either of these tumors reveal elevated antibody titers against EB viral capsid antigens (VCA) and in a high percentage also against E B V early antigens (EA) (Henle et al. 1970a,b). In Burkitt's lymphoma cells, EBV-specific membrane antigens (Gunven et al. 1970) as well as EB-associated nuclear antigens (EBNA) have been demonstrated (Reedman and Klein 1973; Reedman et al. 1974). The transforming potential of E B V for lymphatic cells has been shown in vitro (Henle et al. 1967; Pope et al. 1968). Recently the susceptibility of immunoglobulin-synthesizing lymphocytes has been convincingly demonstrated (Klein et al., unpubl.; Schneider and zur Hausen 1975). It appears that type T lymphocytes lack receptors for E B V absorption (Jondal and Klein 1973). A variety of non-Burkitt type B lymphomas do not contain EBV-specific nucleic acids and antigens (Lindahl et al. 1974), despite the presence of E B V antibodies and the apparent persistence of the virus in cells of the peripheral blood. This provides further indirect evidence for the unique role of E B V in Burkitt's lymphoma. Nasopharyngeal carcinomas contain, in contrast to Burkitt's lymphoma, a mixed cell population. Islands of nonlymphatic epithelial tumor cells are infiltrated to a varying extent by lymphocytes (Shanmugaratnam 1972). The degree of lymphatic infiltration has even been used to subclassify this tumor, which was originally named "lymphoepithelioma." The rather well known "lymphotropism" of E B V suggested to some investigators that the viral D N A demonstrated in these tumors by nucleic acid hybridizations should be located within the infiltrating lymphocytes (McAllister 1973). Thus the nonlymphoid tumor cells would not contain virus-specific products. Previous data from our laboratory were at variance with this interpretation (Wolf et al. 1973). They revealed the presence of viral DNA within epithelial cells of the two tumors examined by in situ hybridizations and anticomplementary immunofluorescence. The following is an extension of these studies which establishes further the presence of EB viral DNA within the tumor cells of nasopharyngeal carcinomas. In addition, the recent induction of lymphoproliferative disease by E B V in marmosets (Shope et al. 1973) and an owl monkey (Epstein et al. 1973) stimulated us to similar experiments. It was our intention to infect primates with virus isolates from different virus-producing lymphoblastoid lines and to demonstrate virus-specific nucleic acids within the tumor material of such animals. The following report summarizes the results.