Patients with Human Immunodeficiency virus (HIV) infection, especially those with AIDS, have an increased risk of development of non-Hodgkin's B-cell lymphomas (NHL) over that seen in the general population. Epstein-Barr Virus (EBV) genome is present in many of these lymphomas. Some of these lymphomas also show evidence of chromosomal translocations similar to those seen in EBV-associated Burkitt's lymphoma (BL) cells. increased expression of EBV proteins and increased production of infectious EBV particles have also been reported in these patients. The recent description of HIV infection of human peripheral blood mononuclear cell-reconstituted SCID (hu-PBMC-SCID) mice and the development of EBV-associated tumors in this animal model offers a system in which to examine both viruses in an in vivo model. The overall objective of this proposal is to investigate the role of cytotoxic T lymphocytes (CTL) in vivo in controlling EBV-induced. lymphoproliferative disorders and examine the role of HIV infection in hu-PBMC-SCID mice on the production of EBV-associated lymphomas. In addition, the role of EBV strain differences in tumor induction and the role of chromosomal abnormalities in HIV-associated tumors will be examined. In order to accomplish these goals the following specific aims will be addressed: 1. To define the immune system components which appear to be lost upon transfer of PBMC to SCID mice resulting in EBV-induced lymphomas. 2. To determine the role of CTL in controlling EBV-associated lymphoproliferation. 3. To determine the effect of acute infection with HIV on the production of tumors in hu-PBMC-SCID mice. 4. To determine any differences in tumor-inducing ability between EBV strains A and B in the SCID mouse model. 5. To evaluate the reconstitution of SCID mice with PBMC from EBV+/HIV-- infected and EBV+/HIV-uninfected donors for the comparison of tumor production between the two groups.
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