Transactivation of human immunodeficiency virus-1 in T-cells by Mycobacterium tuberculosis-infected mononuclear phagocytes.
Worldwide, tuberculosis (TB) is the most frequent coinfection with human immunodeficiency virus-1 (HIV-1), and active TB enhances the progression of HIV-1 disease in dually infected subjects. In the microenvironment of Mycobacterium tuberculosis (MTB)-infected foci, where HIV-1-infected CD4 T-cells come into contact with MTB-infected macrophages, the direct interaction of the two cell types in the activation of latent HIV-1 may be important. In this study we sought to determine whether MTB-infected human primary mononuclear phagocytes-namely, alveolar macrophages (AMs) and their less mature blood precursors, monocytes-activate HIV-1 in a T-cell line stably transfected with an HIV-1 long terminal repeat (LTR) reporter construct (1G5 cells) and induce HIV-1 expression in T-cells from HIV-1-infected subjects. MTB-infected monocytes and AMs, and not Mycobacterium avium-infected cells, activated HIV-1 LTR in 1G5 cells in the presence and absence of HIV-1 tat. Transactivation of HIV-1 LTR by MTB-infected mononuclear phagocytes was mediated mainly by tumor necrosis factor-alpha. In AMs, but not monocytes, membrane tumor necrosis factor-alpha contributed to transactivation of HIV-1 LTR. MTB-infected MNs from 60% of HIV-infected subjects induced HIV-1 LTR in 1G5 cells as well. Furthermore, HIV-1 transcription was induced in autologous T-cells from 30% of the HIV-1-infected subjects. We therefore conclude that MTB-infected mononuclear phagocytes can transactivate HIV-1 in CD4 cells. Transactivation of latent HIV-1 in CD4 T-cells by MTB-infected mononuclear phagocytes may in part be responsible for increased HIV activity at sites of MTB infection during dual infection in vivo.
The Division of Infectious Disease, Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. zxt2@po.cwru.edu
Zahra
Z
Toossi
Mianda
M
Wu
Najmul
N
Islam
Luciella
L
Teixeira-Johnson
Rana
R
Hejal
Htin
H
Aung
D017088:AIDS-Related Opportunistic Infections / Q000235:genetics* / Q000276:immunology / Q000821:virology*; D018791:CD4 Lymphocyte Count; D002478:Cells, Cultured; D005260:Female; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D006801:Humans; D019169:Jurkat Cells; D008297:Male; D009000:Monocytes / Q000382:microbiology; D009169:Mycobacterium tuberculosis; D013601:T-Lymphocytes / Q000821:virology*; D015533:Transcriptional Activation / Q000235:genetics*; D014397:Tuberculosis, Pulmonary / Q000235:genetics* / Q000276:immunology / Q000821:virology*