Epstein-Barr virus infections and their association with human malignancies: some key questions.
Epstein-Barr virus (EBV) expresses genes that stimulate cells to divide in culture. This property, coupled with the close association of the virus with numerous malignancies, has prompted its designation as a human DNA tumour virus. Before human herpesvirus 8 (HHV-8, alternatively KS virus) was discovered, EBV was unique in this property among the human herpesviruses. EBV infection has been best characterised in terms of gene expression in B lymphocytes and epithelium, which represent cells found in the best known of the associated malignancies, Burkitt's lymphoma and poorly differentiated nasopharyngeal carcinoma. The bulk of evidence supports B cells as the primary EBV reservoir with the viral route into other cell types remaining ill-defined. Molecular studies on gene expression in the associated tumours suggest that EBV encodes a number of functions associated with cell growth; whether they are expressed or silent may largely be under control of the host cell. Many questions partly addressed here remain with regard to this virus, two critical ones relating to the mechanisms by which viral gene products escape T-cell recognition - relevant from the fact that gene expression is not tightly restricted to nonimmunogenic functions in tumours - and whether EBV can invoke cell growth in a manner not requiring its continued presence. The latter seems a plausible hypothesis and is of particular importance with regard to identifying and understanding pathologies associated with EBV, as viral transcriptional transactivators may on initial infection permanently perturb cell regulation.
Griffin
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Department of Infectious Diseases (Virology), Imperial College School of Medicine, London, UK. bgriffin@rpms.ac.uk
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D001402:B-Lymphocytes; D002051:Burkitt Lymphoma; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral; D016679:Genome, Viral; D006566:Herpesviridae Infections; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000276:immunology / Q000821:virology*; D014412:Tumor Virus Infections