Commentary. EB virus, infectious mononucleosis, and cancer: the closing of the web.

The web of causation is closing in on EB virus in its relation to certain conditions. In heterophile positive infectious mononucleosis the web of causation seems established beyond any reasonable doubt (1-3). The evidence derived from prospective serological studies that EBV antibody is regularly absent prior to infectious mononucleosis and regularly appears during illness (4-7) is supported by the demonstration of EBV-specific IgM antibody indicative of a primary infection (8-10), by identification of the virus in lymphocytes cultured from the blood (1) by isolation of the virus from the throat ( 1 1-13 ), and by suggestive experimental evidence of infectious mononucleosis in squirrel monkeys (14) and gibbons (15) inoculated with EBV or EBV-infected cells. The immunological events that turn infectious mononucleosis on and turn it off are not so clear, although evidence is rapidly accumu-lating on these questions. Figure 1 presents a working schema of pathogenesis. EB virus appears to enter the oropharynx in young adults, probably thru kissing, and multiplies locally producing a lytic and persistent infection (16). It enters the blood stream and possibly the gut although the latter has not yet been established. Lymphocytes of the B-type are infected and a nonproductive infection of long duration is established. Some of these transformed B cells may contribute early to the atypical lymphocytosis. Current evidence then suggests that there is mixed lymphocyte reponse of T cells to B cells altered by an EBV-membrane induced antigen. This results in T cell proliferation (17), transformation, and a major outpouring of atypical lymphocytes. Lymphocytes from acute cases of infectious mononucleosis have also been found to cause stimulation of convalescent leukocytes from the same