Pathogenesis of HIV-related malignancies

Human immunodeficiency virus (HIV)-1 infection is associated with increased frequency of Kaposi's sarcoma and high-grade B-cell lymphoma. Several other cancers in HIV-1-infected individuals have been reported, although without statistically significant increase in their respective occurrences. Although HIV-1 does not infect either Kaposi's sarcoma-derived spindle cells or B lymphocytes in vivo, viral proteins in vitro have been shown to be mitogenic to both Kaposi's sarcoma-derived spindle cells and B lymphocytes. Furthermore, several cytokines influence directly and indirectly the proliferative differentiation capacity of these cells. These cytokines include interleukin-1, interleukin-4, interleukin-6, and tumor necrosis factor. Many of these cytokines also are regulated by HIV-1 infection of T lymphocytes and monocyte/macrophage. Furthermore, elevated levels of interleukin-1, interleukin-6 and tumor necrosis factor have been observed in patients with HIV-1 infection, particularly in advanced stages, when these tumors often manifest. Thus, it appears that although HIV-1 does not directly transform cells permissive to its infection, viral proteins directly and through regulation of cellular genes exert activities that may lead to the development of Kaposi's sarcoma and B-cell lymphoma.