title: Phagocytosis of Mycobacterium tuberculosis modulates human immunodeficiency virus replication in human monocytic cells.
abstract: Macrophage activation resulting from phagocytosis has the potential to modulate human immunodeficiency virus (HIV) replication. We have determined the effects of phagocytosis of particulate stimuli on transcription and release of HIV. Using THP-1 and Mono Mac 6 human monocytic cell lines transfected with HIV long terminal repeat sequence chloramphenicol acetyltransferase (LTR CAT) constructs we have demonstrated that phagocytosis of Mycobacterium tuberculosis enhanced HIV-1 and -2 LTR CAT expression. However phagocytosis of zymosan or inert latex beads had little or no effect on CAT expression. Enhancement of HIV LTR CAT expression was dependent upon intact NF-kappa B binding sites and was independent of tumour necrosis factor alpha secretion. M. tuberculosis strains of different degrees of virulence induced similar levels of enhanced CAT expression. In contrast, phagocytosis of M. tuberculosis by HIV-1-infected THP-1 cells reduced supernatant reverse transcriptase (RT) activity without suppression of p24 antigen release. Phagocytosis of zymosan granules or latex particles did not alter released RT activity. However, phagocytosis of either M. tuberculosis, zymosan granules or latex particles by HIV-1-infected human peripheral blood monocyte-derived macrophages reduced supernatant RT activity. These data indicate that phagocytosis of M. tuberculosis may enhance HIV transcription in monocytic cells although it may reduce release of intact HIV.
authors.affiliation: Division of Communicable Diseases, St George's Hospital Medical School, Tooting, London, U.K.
authors.forename: R J
authors.initials: RJ
authors.lastname: Shattock
authors.forename: J S
authors.initials: JS
authors.lastname: Friedland
authors.forename: G E
authors.initials: GE
authors.lastname: Griffin
mesh_terms: D000911:Antibodies, Monoclonal; D002460:Cell Line; D016655:HIV Core Protein p24 / Q000032:analysis; D016325:HIV Long Terminal Repeat / Q000235:genetics / Q000276:immunology; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000502:physiology*; D015498:HIV-2 / Q000502:physiology*; D006801:Humans; D008262:Macrophage Activation / Q000502:physiology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology*; D008863:Microspheres; D009000:Monocytes / Q000276:immunology / Q000382:microbiology*; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D009500:Neutralization Tests; D010587:Phagocytosis / Q000502:physiology*; D012194:RNA-Directed DNA Polymerase / Q000032:analysis; D014158:Transcription, Genetic / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014774:Virulence; D014779:Virus Replication / Q000276:immunology; D015054:Zymosan
chemical_list: D000911:Antibodies, Monoclonal; D016655:HIV Core Protein p24; D014409:Tumor Necrosis Factor-alpha; D015054:Zymosan; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase