Dioxin activates human immunodeficiency virus-1 expression in chronically infected promonocytic U1 cells by enhancing NF-kappa B activity and production of tumor necrosis factor-alpha.
Dioxin, a prevalent environmental pollutant, is known to enhance replication of viruses in animals, but the mechanism is poorly understood. Here we report that dioxin triggers human immunodeficiency virus-1 (HIV-1) gene expression, resulting in increased production of HIV in chronically infected promonocytic U1 cells. This effect of dioxin is mediated, in part, via activation of nuclear factor kappa-B (NF-kappa B), a key cellular transcription factor that plays an important role in the induction of HIV genes and cytokine genes that regulate HIV-replication. Dioxin stimulated the production of tumor necrosis-alpha in U1 cells, and pentoxifylline, an inhibitor of TNF-alpha synthesis, inhibited dioxin induced HIV production and TNF-alpha. These studies provide a molecular and cellular basis for increased viral replication in cells exposed to dioxin.
Gollapudi
S
S
University of California at Irvine 92717, USA.
Kim
C H
CH
Patel
A
A
Sindhu
R
R
Gupta
S
S
D001483:Base Sequence; D001665:Binding Sites; D002470:Cell Survival / Q000187:drug effects; D004147:Dioxins / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D005814:Genes, Viral; D016655:HIV Core Protein p24 / Q000032:analysis / Q000096:biosynthesis; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D015345:Oligonucleotide Probes; D010431:Pentoxifylline / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D014779:Virus Replication / Q000187:drug effects*
D004147:Dioxins; D016655:HIV Core Protein p24; D016328:NF-kappa B; D015345:Oligonucleotide Probes; D014409:Tumor Necrosis Factor-alpha; D010431:Pentoxifylline