Viable Mycobacterium avium is required for the majority of human immunodeficiency virus-induced upregulation in monocytoid cells.
The Mycobacterium avium complex (MAC), an intracellular pathogen of cells of the macrophage lineage, often clinically coexists with human immunodeficiency virus type 1 (HIV). It was shown previously that coinfection of the monocytoid cell line U937 with HIV and MAC results in the enhancement of HIV replication. To determine whether MAC-mediated HIV upregulation is due to the exposure of intact organisms to HIV-infected cells or if actual infection with viable organisms is required for the effect, U937 cells were coinfected simultaneously with HIV and live or heat-killed MAC. Live MAC (infection) consistently increased HIV reverse transcriptase (RT) activity by more than 3-fold. Heat-killed MAC, however, failed to enhance RT activity significantly. Further investigation showed that infection of U38 cells [a U937-derived cell line containing regions of the HIV-1 long terminal repeat (LTR) linked to chloramphenicol acetyl transferase (CAT)] with live or heat-killed MAC resulted in a similar enhancement of HIV LTR-CAT transcription. In addition, transient transfection of U937 cells with a full-length wild-type HIV LTR-CAT construct revealed that heat-killed MAC stimulated LTR-mediated CAT activity to levels comparable to those of viable MAC. Finally, both live and heat-killed MAC mediated similar enhancement of NF-kappa B DNA-binding activity. Taken together, these observations confirm previous findings that MAC-induced NF-kappa B-dependent LTR-CAT activity is not a major factor in upregulating HIV expression in a coinfection model. It also indicates that MAC infection plays a significant role in the enhancement of HIV replication and suggests that viable MAC either contains or induces the production of an as-yet-unidentified factor(s) that mediates the enhancement of HIV replication.
Ghassemi
Mahmood
M
Department of Medicine, University of Illinois, 808 S. Wood St, Chicago, IL 60612, USA.
Novak
Richard M
RM
Department of Medicine, University of Illinois, 808 S. Wood St, Chicago, IL 60612, USA.
Khalili
Mohammad F
MF
Department of Medicine, University of Illinois, 808 S. Wood St, Chicago, IL 60612, USA.
Zhou
Jian
J
Department of Medicine, University of Illinois, 808 S. Wood St, Chicago, IL 60612, USA.
D024202:Electrophoretic Mobility Shift Assay; D015658:HIV Infections / Q000276:immunology / Q000382:microbiology* / Q000821:virology; D016325:HIV Long Terminal Repeat / Q000276:immunology; D054303:HIV Reverse Transcriptase / Q000276:immunology / Q000378:metabolism; D015497:HIV-1 / Q000201:enzymology / Q000276:immunology / Q000502:physiology*; D006801:Humans; D015269:Mycobacterium avium Complex / Q000502:physiology*; D015270:Mycobacterium avium-intracellulare Infection / Q000276:immunology / Q000382:microbiology / Q000821:virology*; D016328:NF-kappa B / Q000276:immunology; D020298:U937 Cells; D015854:Up-Regulation; D014779:Virus Replication / Q000276:immunology
D016328:NF-kappa B; D054303:HIV Reverse Transcriptase