Viable Mycobacterium avium is required for the majority of human immunodeficiency virus-induced upregulation in monocytoid cells.

Abstract

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.

• Authors: Mahmood Ghassemi, Richard M Novak, Mohammad F Khalili, Jian Zhou
• Journal: Journal of medical microbiology (J Med Microbiol) Vol. 52 Issue Pt 10 Pg. 877-882 (Oct 2003) ISSN: 0022-2615 [Print] England
• PMID: 12972581 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• NF-kappa B
• HIV Reverse Transcriptase

Topics

• Electrophoretic Mobility Shift Assay
• HIV Infections (immunology, microbiology, virology)
• HIV Long Terminal Repeat (immunology)
• HIV Reverse Transcriptase (immunology, metabolism)
• HIV-1 (enzymology, immunology, physiology)
• Humans
• Mycobacterium avium Complex (physiology)
• Mycobacterium avium-intracellulare Infection (immunology, microbiology, virology)
• NF-kappa B (immunology)
• U937 Cells
• Up-Regulation
• Virus Replication (immunology)