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Epstein-Barr Virus Herpesviruses • Epstein-Barr = 1 of 8 • Genetically stable, large DNA genomes Herpesviruses • Epstein-Barr = 1 of 8 • Genetically stable, large DNA genomes • STABILITY: slowly co-evolved • Teach a lot about human immunity Discovery • Antony Epstein attended lecture, 1961 • Surgeon working in Kampala Discovery • Antony Epstein attended lecture, 1961 • Surgeon working in Kampala • “Hitherto unrecognised symptom” caused most common childrens’ cancer in Africa • 1964 = observed herpesviruses in cultured lymphoma cells Discovery • Collaboration with scientists in Philadelphia • Viral capsid antigens Discovery • Seroepidemiological studies implicated virus in several cancers Discovery • Seroepidemiological studies implicated virus in several cancers • Technician developed infectious mononucleosis (glandular fever), 1967 • Observed that she developed antibodies after illness Summary of Discovery 1. Glandular fever Summary of Discovery 2. Cancers Hodgkin’s lymphoma Burkitt’s lymphoma Virus life cycle • Latent (lysogenic) and lytic phases Several viral proteins Infective virions Few viral proteins EBV life cycle EBV life cycle Salivary epithelial cells B-lymphocyte cells EBV life cycle Salivary epithelial cells B-lymphocyte cells Different ‘fates’ EBV life cycle Salivary epithelial cells B-lymphocyte cells Different ‘fates’ - Location - Differentiation status EBV life cycle Salivary epithelial cells B-lymphocyte cells Lytic cycle Memory Nasopharyngeal system Peripheral circulation Thorley-Lawson (2001) Nasopharyngeal system Peripheral circulation Thorley-Lawson (2001) Occasionally Nasopharyngeal system Peripheral circulation Thorley-Lawson (2001) Nasopharyngeal system Peripheral circulation Thorley-Lawson (2001) Symptoms of EBV infection • Primary infection: – Childhood = asymptomatic Symptoms of EBV infection • Primary infection: – Childhood = asymptomatic – Adolescence = 35-60% Infectious mononuelceosis (glandular fever) Glandular fever • • • • Fever Sore throat Swollen spleen Swollen lymph nodes • Rash • Fatigue Persistent infection • >90% of adults are seropositive • Reactivation: 6% of previous sufferers become ill again, due to poor immunity Occasionally Nasopharyngeal system Peripheral circulation Thorley-Lawson (2001) EBV in cancer • EBV linked to tumours in both epithelial and lymphoid tissues • Post-transplant lymphoma – T-cell suppressive drugs – EBV-transformed B-cells grow into tumours EBV in cancer • EBV linked to tumours in both epithelial and lymphoid tissues • Post-transplant lymphoma – T-cell suppressive drugs – EBV-transformed B-cells grow into tumours • AIDS EBV in cancer • EBV linked to tumours in both epithelial and lymphoid tissues • Post-transplant lymphoma – T-cell suppressive drugs – EBV-transformed B-cells grow into tumours • AIDS • Burkitt lymphoma, nasopharyngeal carcinosis, Hodgkin’s lymphoma Key points • Stable relationship with human immune system Key points • Stable relationship with human immune system • EBV evolved access to specific long-lived compartment of B-cells in periphery blood (Joseph et al., 2000, J. Immunol. 165: 2975-2981) Key points • Stable relationship with human immune system • EBV evolved access to specific long-lived compartment of B-cells in periphery blood (Joseph et al., 2000, J. Immunol. 165: 2975-2981) • EBV causes massive lymphocytosis + is very oncogenic Glandular fever Cancer Thank you :-)
