CD8+ T cell suppressor factors and the control of infection, replication and transcription of human immunodeficiency virus.
CD8+ T cells have been shown to produce factors which modulate HIV-1 replication in both T cells and monocytic cells. Examination of the literature reveals that this modulation may occur by the production of beta-chemokines which block viral entry. However, another CD8+ T cell-derived factor(s) targets the replication of HIV-1 at the level of transcription. CD8+ T cell factors strongly suppress replication at the level of transcription in T cells and T cell lines, the factors enhance both replication and transcription in cells of the monocyte/macrophage lineage. The enhancement of transcription and replication, which is pertussis toxin sensitive is induced by increased production of TNF-alpha by the target cells. Thus, CD8+ T cells produce factors which mediate effects on transcription and replication of HIV-1 in a cell type-dependent manner. In this review a summary of the effects of chemokines and CD8-derived factors on HIV-1 transcription and replication is presented focusing on the cellular pathways which may mediate their effects on HIV transcription and replication in different cell types. The virus-host cell interactions that participate in the persistent replication of HIV in macrophages and the suppression of these functions in T cells require definition. The identification of CD8+ T cell factors which exert these controls on HIV-1 may lead to promising new therapies for HIV infection.
Centre for Molecular Medicine, Ottawa Hospital Research Institute, Ontario, Canada. kcopeland@ogh.on.ca
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Copeland
D019380:Anti-HIV Agents / Q000009:adverse effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D018925:Chemokines / Q000096:biosynthesis; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D009000:Monocytes / Q000276:immunology / Q000821:virology; D013491:Suppressor Factors, Immunologic / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D014158:Transcription, Genetic; D014779:Virus Replication
D019380:Anti-HIV Agents; D018925:Chemokines; D013491:Suppressor Factors, Immunologic