The interaction of monocyte chemoattractant protein-1 and tumour necrosis factor-alpha in Mycobacterium tuberculosis-induced HIV-1 replication at sites of active tuberculosis.
Tuberculosis (TB) is a prominent opportunistic infection in HIV-1-infected subjects and enhances HIV-1 replication. TB is associated with excess monocyte chemoattractant protein (MCP)-1 and tumour necrosis factor (TNF)-alpha activity in situ, both of which are implicated in transcriptional activation of HIV-1. The role of MCP-1 and TNF-alpha in activation of HIV-1 during TB and by Mycobacterium tuberculosis (MTB) in mononuclear cells from HIV-1/TB subjects with pleural TB was examined here. Extremely high levels of MCP-1 (as compared with TNF-alpha) protein and mRNA were found in pleural fluid and pleural fluid mononuclear cells. Levels of MCP-1 mRNA were sustained during in vitro culture of pleural fluid mononuclear cells. Neutralization of MCP-1 (but not TNF-alpha), resulted in inhibition of MTB induced HIV-1 gag/pol mRNA. Neutralization of both MCP-1 and TNF-alpha, however, abrogated the effect of anti-MCP-1 antibody on HIV-1 mRNA. LMP-420, a small molecular transcriptional inhibitor of both TNF-alpha and MCP-1 expression, did not reduce MTB-induced HIV-1 expression. These data imply that MCP-1 activity may be critical to activation of HIV-1 at sites of TB. An interplay of MCP-1 and TNF-alpha is also suggested.
Case Western Reserve University, Cleveland, OH 44106, USA.
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H
Mayanja-Kizza
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M
Wu
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H
Aung
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S
Liu
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H
Luzze
C
C
Hirsch
Z
Z
Toossi
D017088:AIDS-Related Opportunistic Infections / Q000276:immunology / Q000378:metabolism*; D000328:Adult; D018932:Chemokine CCL2 / Q000276:immunology / Q000378:metabolism*; D004279:DNA, Viral / Q000032:analysis; D015658:HIV Infections / Q000150:complications / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D009169:Mycobacterium tuberculosis; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014376:Tuberculosis / Q000150:complications / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*; D014775:Virus Activation / Q000502:physiology*; D014779:Virus Replication
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D004279:DNA, Viral; D012333:RNA, Messenger; D012367:RNA, Viral; D014409:Tumor Necrosis Factor-alpha