Interleukin 6 induces human immunodeficiency virus expression in infected monocytic cells alone and in synergy with tumor necrosis factor alpha by transcriptional and post-transcriptional mechanisms.
The immunoregulatory cytokine interleukin 6 (IL-6) directly upregulates production of human immunodeficiency virus (HIV) in acutely as well as in chronically infected cells of monocytic lineage. In addition, IL-6 synergizes with tumor necrosis factor alpha (TNF-alpha) in the induction of latent HIV expression. Unlike TNF-alpha, upregulation of viral expression induced by IL-6 alone does not occur at the transcriptional level and it is not associated with accumulation of HIV RNA. However, when IL-6 and TNF-alpha synergistically stimulate HIV production, accumulation of HIV RNA and increased transcription are observed, indicating that IL-6 affects HIV expression at multiple (transcriptional and post-transcriptional) levels.
Laboratories of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
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G
Poli
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P
Bressler
A
A
Kinter
E
E
Duh
W C
WC
Timmer
A
A
Rabson
J S
JS
Justement
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S
Stanley
A S
AS
Fauci
D015152:Blotting, Northern; D015153:Blotting, Western; D002460:Cell Line; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D004357:Drug Synergism; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects / Q000254:growth & development*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D009000:Monocytes / Q000382:microbiology*; D012367:RNA, Viral / Q000096:biosynthesis; D011994:Recombinant Proteins; D012191:Retroviridae Proteins / Q000096:biosynthesis*; D014158:Transcription, Genetic / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014775:Virus Activation / Q000187:drug effects*
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D015850:Interleukin-6; D012367:RNA, Viral; D011994:Recombinant Proteins; D012191:Retroviridae Proteins; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor