title: Human immunity against EBV-lessons from the clinic.
abstract: The mammalian immune system has evolved over many millennia to be best equipped to protect the host from pathogen infection. In many cases, host and pathogen have coevolved, each acquiring sophisticated ways of inducing or protecting from disease. Epstein-Barr virus (EBV) is a human herpes virus that infects >90% of individuals. Despite its ubiquity, infection by EBV is often subclinical; this invariably reflects the necessity of the virus to preserve its host, balanced with sophisticated host immune mechanisms that maintain viral latency. However, EBV infection can result in various, and often fatal, clinical sequelae, including fulminant infectious mononucleosis, hemophagocytic lymphohistiocytosis, lymphoproliferative disease, organomegaly, and/or malignancy. Such clinical outcomes are typically observed in immunosuppressed individuals, with the most extreme cases being Mendelian primary immunodeficiencies (PIDs). Although these conditions are rare, they have provided critical insight into the cellular, biochemical, and molecular requirements for robust and long-lasting immunity against EBV infection. Here, we review the virology of EBV, mechanisms underlying disease pathogenesis in PIDs, and developments in immune cell-mediated therapy to treat disorders associated with or induced by EBV infection.
authors.affiliation: Immunology Division, Garvan Institute of Medical Research, Darlinghurst 2010, NSW, Australia s.tangye@garvan.org.au.|St. Vincent's Clinical School, University of New South Wales, Sydney 2052, NSW, Australia.
authors.forename: Stuart G
authors.identifier: 0000-0002-5360-5180
authors.initials: SG
authors.lastname: Tangye
authors.affiliation: Centenary Institute, University of Sydney, Newtown 2042, NSW, Australia.
authors.forename: Umaimainthan
authors.identifier: 0000-0002-1113-3306
authors.initials: U
authors.lastname: Palendira
authors.affiliation: Immunology Division, Garvan Institute of Medical Research, Darlinghurst 2010, NSW, Australia.|St. Vincent's Clinical School, University of New South Wales, Sydney 2052, NSW, Australia.
authors.forename: Emily S J
authors.identifier: 0000-0002-0240-4370
authors.initials: ES
authors.lastname: Edwards
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D053282:CD27 Ligand / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000209:etiology; D016219:Immunotherapy, Adoptive; D007694:Killer Cells, Natural / Q000276:immunology; D008232:Lymphoproliferative Disorders / Q000235:genetics; D015398:Signal Transduction; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein / Q000235:genetics; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000502:physiology
chemical_list: D053282:CD27 Ligand; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7