B cells and herpesviruses: a model of lymphoproliferation.
Unlike alpha- and beta-herpesviruses, human gamma-herpesviruses, including the Epstein-Barr virus (EBV) and the human herpesvirus-8 (HHV-8), are B lymphotropic viruses. Primary infection with EBV, in otherwise healthy subjects, causes a benign lymphoproliferative syndrome, the mononucleosis syndrome. However, several epidemiologic and biologic studies have shown a pathogenetic role of EBV in the development of human B cell lymphomas, both in immunocompetent and in immunosuppressed individuals. HHV-8 is the necessary etiologic agent of a lymph vascular tumor, the Kaposi sarcoma, but it is also implicated in the pathogenesis of rare B cell lymphoproliferative disorders, mainly occurring in the setting of immunosuppression. The aim of this review is to provide an updated description of the different strategies used by these two herpesviruses to influence B cell fate decisions. Both EBV and HHV-8 have evolved specific mechanisms in order to: (1) interact with the B cell developmental machinery; (2) allow infected B cells to escape from the control of the immune system; (3) affect the B cell cycle checkpoints; (4) mimic and influence B cellular proliferation and differentiation pathways. Understanding the mechanisms of herpesvirus induced B cell lymphoproliferation will provide the basis for novel treatment approaches in patients with EBV and HHV-8 related lymphomas.
Department of Oncology and Hematology, University of Modena and Reggio Emilia, Modena, Italy.
Patrizia
P
Barozzi
Leonardo
L
Potenza
Giovanni
G
Riva
Daniela
D
Vallerini
Chiara
C
Quadrelli
Raffaella
R
Bosco
Fabio
F
Forghieri
Giuseppe
G
Torelli
Mario
M
Luppi
D000956:Antigens, Viral / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D006566:Herpesviridae Infections / Q000276:immunology* / Q000821:virology; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D006801:Humans; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000821:virology; D008232:Lymphoproliferative Disorders / Q000276:immunology* / Q000821:virology; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism
D000956:Antigens, Viral; D051880:Receptors, Notch; D051153:Wnt Proteins