157 Pathogenesis of Epstein-Barr Virus-driven lymphomas of HIV+ patients

Autor: Riccardo Dolcetti
Rok vydání: 2014
Předmět:
Zdroj: Journal of Acquired Immune Deficiency Syndromes (1999)
ISSN: 1525-4135
Popis: Human Immunodeficiency Virus (HIV)+ patients have an increased risk to develop lymphomas, including a significant fraction of histotypes associated with Epstein-Barr Virus (EBV) infection. Although restoration of EBV-specific T-cell function induced by HAART has led to a decreased incidence of the more immunogenic EBV-associated lymphomas, such as immunoblastic and primary central nervous system lymphomas, other EBV+ histotypes are still prevalent in the HAART era, particularly Hodgkin’s lymphoma. Therefore, factors other than HIV-induced immune suppression are probably required for the development of EBV-related lymphomas in this setting. Particular attention is being given to the identification of microenvironmental stimuli able to up-regulate critical EBV latency proteins or to induce/enhance EBV replication. In fact, recent evidence indicates that, although latency programs predominate in EBV-driven tumors, lytic EBV replication may also be of pathogenic relevance, at least in the early phases of cell transformation. This is particularly relevant for HIV-related lymphomagenesis since the underlying impairment of immune responses may favour uncontrolled activation of EBV lytic replication in latently-infected B lymphocytes. Available data indicate that local expression of distinct cytokines, including IL-4 and IL-13, may up-regulate the expression of the LMP-1 oncoprotein in B cells, thus favoring lymphomagenesis. In the search of microenvironmental factors that may promote the development of EBV-driven lymphomas in HIV+ patients, we obtained evidence supporting a pathogenic role for HIV matrix protein p17, which accumulates in lymphoid tissues of HIV+ individuals, even during HAART. Our findings support a direct contribution of HIV p17 to the development of EBV-driven lymphomagenesis and may provide the rationale for new strategies of clinical intervention in this setting.
Databáze: OpenAIRE