Physicochemical-viral synergism during Epstein-Barr virus infection: a review.
Infection with the Epstein-Barr virus (EBV), a ubiquitous herpesvirus, may be asymptomatic or may result in any one of a number of mild to severe hematopoietic disorders. Besides causing infectious mononucleosis, EBV has been associated with 95% of endemic African Burkitt's lymphoma and 10%-20% of the sporadic form of Burkitt's lymphoma outside Africa. EBV has also now been associated with all histological forms of nasopharyngeal carcinoma. During the acute phase of infectious mononucleosis, a surprisingly large number of EBV-infected cells can be detected in the peripheral circulation (up to 0.05%). EBV also replicates in epithelial cells in the oropharyngeal region. It is known that physicochemical carcinogens can act synergistically with tumor viruses to enhance both viral replication and cellular transformation. Several laboratories have shown that chemical carcinogens and, in particular, DNA-alkylating agents can enhance EBV replication, EBV-induced lymphocyte transformation, and EBV-associated malignant conversion. Since there are approximately 10(12) lymphocytes in an adult, the large number of EBV-infected cells present in the circulation and oropharynx during infection would present an extraordinarily large target for carcinogen interaction. Moreover, after infection, EBV remains latent in lymphoid cells for life. When these findings are considered in light of analytical and descriptive epidemiological evidence suggesting that, in addition to EBV infection, other environmental cofactors are important in EBV-associated tumor formation, the question could be asked whether these cofactors are physicochemical carcinogens. In an attempt to answer this question, I will review the ways in which physicochemical carcinogens can influence viral replication and virally induced transformation; aspects of the biology of the EBV-lymphocyte-epithelial cell interaction that make this system perhaps unique in terms of possible physicochemical interactions; the epidemiological and experimental evidence supporting EBV-physicochemical carcinogen synergisms; and finally, possible mechanisms whereby chemicals could influence the outcome of EBV infection and the probability of these events occurring during naturally acquired EBV infection.
Henderson
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Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA 19140.
D002051:Burkitt Lymphoma / Q000209:etiology; D002273:Carcinogens; D002472:Cell Transformation, Viral / Q000187:drug effects; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000209:etiology; D014779:Virus Replication / Q000187:drug effects
D002273:Carcinogens