High grade B cell non-Hodgkin's lymphoma (NHL-B) is a major neoplastic sequelae of infection with the AIDS virus, HIV-1. AIDS-related lymphomas (ARL) have been considered to be secondary to the immune deficiency state induced by HIV, although the direct involvement of HIV or other viruses such as EBV have not as yet been demonstrated. We have recently studied two patients with ARL that presented with a previously unreported histopathologic """"""""syncytial variant"""""""" of Burkitt's (small non cleaved B cell) lymphoma. Cell lines were derived from these ARL which have been shown to contain retroviral particles on ultrastructural analysis, and reverse transcriptase (RT) activity in culture supernatants. In this proposal, we will isolate, characterize, and molecularly clone the ARL-associated human retroviruses (ARL-RV). It will be determined if the ARL-RV are related to the HIV subfamily of non-transforming lentiviruses associated with immune deficiency or possibly to the transforming HTLV subfamily oncoviruses. Alternatively, these viruses could represent previously unknown human retroviruses or represent recombinant retroviruses involving known and/or unknown retroviruses. We will also determine the species and host range of infectivity for normal and neoplastic cells in vitro. The SCIDHu murine model will be utilized in vivo to assess the potential of the ARL-RV for inducing neoplasia and/or immune deficiency. Other studies will determine the biologic activity (CPE, syncytia formation, cell immortalization in vitro, etc.) associated with these viruses. Finally, we will utilize the molecular clones and immunologic regents generated in our studies to determine the presence and distribution of the ARL-RV in ARL, non-AIDS NHL- B, and other populations believed to be at risk for lymphoma including iatrogenically immunosuppressed organ transplant recipients, intravenous drug abusers, etc. These studies should indicate whether the ARL-RV can play a significant role in the pathogenesis of ARL, or possibly in lymphomagenesis in general, and provide at least a preliminary indication of the presence of this retrovirus in various subsets of the human population.
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