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.
Gill
P S
PS
University of Southern California School of Medicine, Los Angeles.
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications; D001402:B-Lymphocytes / Q000473:pathology; D002455:Cell Division; D016207:Cytokines / Q000096:biosynthesis / Q000502:physiology; D005260:Female; D015967:Gene Expression Regulation, Viral; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D015994:Incidence; D008228:Lymphoma, Non-Hodgkin / Q000453:epidemiology / Q000209:etiology*; D008297:Male; D014411:Neoplastic Stem Cells / Q000473:pathology; D012191:Retroviridae Proteins / Q000502:physiology; D012514:Sarcoma, Kaposi / Q000453:epidemiology / Q000209:etiology*
D016207:Cytokines; D012191:Retroviridae Proteins