Role of placental cytokines in transcriptional modulation of HIV type 1 in the isolated villous trophoblast.
During pregnancy, a complex cytokine network is present at the maternal-fetal interface in order to support normal growth and development of the placenta and fetus. HIV can frequently infect placental trophoblast but the impact of cytokines produced locally by the placenta and decidua on virus expression and replication is unknown. We comprehensively assayed the cytokines typically present in the placental microenvironment for their potential to modulate HIV transcriptional activation in the isolated trophoblast cells employing a transient transfection assay with luciferase as a reporter gene. Long terminal repeats (LTRs) of two divergent virus strains, HIV-1 LAI and HIV-1 NDK, were used to analyze virus-specific features. Four cytokines, epidermal growth factor (EGF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 1 beta (IL-1 beta), and tumor necrosis factor alpha (TNF-alpha), were found to stimulate promoters of both viruses, whereas interferon alpha (IFN-alpha) and IFN-beta were found to suppress the transcription driven from both promoters. The differences observed between the two viruses did not reach a statistically significant level. None of the remaining cytokines, including EGF; GM-CSF; insulin-like growth factor I (IGF-I); IFN-alpha, IFN-beta, and IFN-gamma; IL-1 alpha, IL-1 beta, IL-2, IL-6, and IL-10; leukemia inhibitory factor (LIF); macrophage colony-stimulating factor (M-CSF); platelet-derived growth factor BB (PDGF-BB); transforming growth factor beta (TGF-beta); and TNF-alpha, affected transcriptional expression of the promoter constructs. Our results demonstrate that the local balance of cytokines may be critical for activation of HIV in the syncytiotrophoblast-cytotrophoblast layer and thus play an important role in the transmission of virus across the placental barrier.
Department of Health Science and Technology, Aalborg University, 8000 Aarhus C, Denmark. vladimir@lsr.auc.dk
Vladimir
V
Zachar
Trine
T
Fink
Uffe
U
Koppelhus
Peter
P
Ebbesen
D001483:Base Sequence; D016207:Cytokines / Q000502:physiology*; D004279:DNA, Viral; D005260:Female; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D010920:Placenta / Q000378:metabolism*; D012689:Sequence Homology, Nucleic Acid; D015533:Transcriptional Activation / Q000502:physiology*; D014327:Trophoblasts / Q000821:virology*
D016207:Cytokines; D004279:DNA, Viral