Lipopolysaccharide is a potent monocyte/macrophage-specific stimulator of human immunodeficiency virus type 1 expression.
Lipopolysaccharide (LPS) potently stimulates human immunodeficiency virus type 1-long terminal repeat (HIV-1-LTR) CAT constructs transfected into monocyte/macrophage-like cell lines but not a T cell line. This effect appears to be mediated through the induction of nuclear factor kappa B (NF-kappa B). Electrophoretic mobility shift assays demonstrate that LPS induces a DNA binding activity indistinguishable from NF-kappa B in U937 and THP-1 cells. LPS is also shown to dramatically increase HIV-1 production from a chronically infected monocyte/macrophage-like cloned cell line, U1, which produces very low levels of HIV-1 at baseline. The stimulation of viral production from this cell line occurs only if these cells are treated with granulocyte/macrophage colony-stimulating factor (GM-CSF) before treatment with LPS. This stimulation of HIV-1 production is correlated with an increase in the level of HIV-1 RNA and and activation of NF-kappa B. LPS is not able to induce HIV-1 production in a cloned T cell line. The effect of LPS on HIV-1 replication occurs at picogram per milliliter concentrations and may be clinically significant in understanding the variability of the natural history of HIV-1 infection.
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142.
R J
RJ
Pomerantz
M B
MB
Feinberg
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D
Trono
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D
Baltimore
D001483:Base Sequence; D002460:Cell Line; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004742:Enhancer Elements, Genetic; D004926:Escherichia coli; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000382:microbiology*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects / Q000382:microbiology*; D016328:NF-kappa B; D010957:Plasmids; D012367:RNA, Viral / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D013601:T-Lymphocytes / Q000187:drug effects / Q000382:microbiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection / Q000235:genetics; D014775:Virus Activation / Q000187:drug effects* / Q000235:genetics
D003115:Colony-Stimulating Factors; D004268:DNA-Binding Proteins; D006133:Growth Substances; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012367:RNA, Viral; D014157:Transcription Factors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor