title: Epstein-Barr virus-driven lymphomagenesis in the context of human immunodeficiency virus type 1 infection.
abstract: Epstein-Barr virus (EBV) is a ubiquitous human γ-herpes virus which establishes a life-long asymptomatic infection in immunocompetent hosts. In human immunodeficiency virus type 1 (HIV-1) infected patients, the impaired immunosurveillance against EBV may favor the development of EBV-related diseases, ranging from lymphoproliferative disorders to B cell non-Hodgkin's lymphomas (NHL). Antiretroviral therapy (ART) has significantly modified the natural course of HIV-1 infection, resulting in decreased HIV-1 plasmaviremia, increased CD4 lymphocytes, and decreased opportunistic infections, indicating a restoration of immune functions. However, the impact of ART appears to be less favorable on EBV-related malignancies than on other AIDS-defining tumors, such as Kaposi's sarcoma, and NHL remains the most common cancer during the ART era. EBV-driven tumors are associated with selective expression of latent oncogenic proteins, but uncontrolled lytic cycle with virus replication and/or reactivation may favor cell transformation, at least in the early phases. Several host's factors may promote EBV reactivation and replication; besides immunodepression, inflammation/chronic immune stimulation may play an important role. Microbial pathogen-associated molecular patterns and endogenous damage-associated molecular patterns, through Toll-like receptors, activate the immune system and may promote EBV reactivation and/or polyclonal expansion of EBV-infected cells. A body of evidence suggests that chronic immune stimulation is a hallmark of HIV-1 pathogenesis and may persist even in ART-treated patients. This review focuses on lymphomagenesis driven by EBV both in the context of the natural history of HIV-1 infection and in ART-treated patients. Understanding the mechanisms involved in the expansion of EBV-infected cells is a premise for the identification of prognostic markers of EBV-associated malignancies.
authors.affiliation: Viral Oncology Unit and AIDS Reference Center, Section of Oncology and Immunology, Department of Surgery, Oncology and Gastroenterology, University of Padova Padova, Italy.
authors.forename: Maria R
authors.initials: MR
authors.lastname: Petrara
authors.forename: Riccardo
authors.initials: R
authors.lastname: Freguja
authors.forename: Ketty
authors.initials: K
authors.lastname: Gianesin
authors.forename: Marisa
authors.initials: M
authors.lastname: Zanchetta
authors.forename: Anita
authors.initials: A
authors.lastname: De Rossi
keywords: B cell activation; EBV; EBV lytic reactivation; EBV-related malignancies; HIV-1; antiretroviral therapy; chronic immune activation