B lymphocytes and Epstein-Barr virus: the lesson of post-transplant lymphoproliferative disorders.
Epstein-Barr virus (EBV) is a ubiquitous human gamma-herpes virus that establishes a life-long asymptomatic infection in immunocompetent hosts by colonizing memory B lymphocytes and hijacking cellular signaling pathways that regulate antigen-dependent B-cell activation and differentiation. In patients with solid organ or hematopoietic stem cell transplantation, the defect in EBV-specific immune responses may allow the outgrowth of EBV-carrying B lymphocytes that may give rise to a spectrum of different clinico-pathologic entities encompassed by the term post-transplantation lymphoproliferative disorders (PTLD). EBV-driven immortalization of B-cells is mediated by the cooperative activity of viral proteins that derange critical cellular pathways controlling growth and/or survival of B lymphocytes. Full transformation of infected B-cells is achieved by the contribution of poorly defined additional co-factors, including microenvironmental stimuli, genetic and epigenetic alterations. The quantification of circulating EBV DNA and EBV-specific T cells are valuable tools in the clinical monitoring of EBV-associated PTLD. The recent advances in elucidation of the mechanisms underlying EBV-induced growth transformation will be instrumental in guiding the design of novel approaches for the treatment of these often life-threatening lymphoproliferative disorders.
Dolcetti
Riccardo
R
Immunovirology and Biotherapy Unit, Department of Pre-Clinical and Epidemiological Research C.R.O. - I.R.C.C.S., National Cancer Institute, 33081 Aviano (PN), Italy. rdolcetti@cro.it
D000956:Antigens, Viral / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004279:DNA, Viral / Q000032:analysis; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000276:immunology / Q000821:virology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D004854:Herpesvirus 4, Human / Q000276:immunology / Q000502:physiology*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000821:virology*; D008232:Lymphoproliferative Disorders / Q000150:complications / Q000276:immunology / Q000821:virology*; D016377:Organ Transplantation / Q000009:adverse effects*; D019562:Viral Load; D014775:Virus Activation
D000956:Antigens, Viral; D016207:Cytokines; D004279:DNA, Viral