Production of Interferons and β-Chemokines by Placental Trophoblasts of HIV-1-Infected Women

Objective: The mechanism whereby the placental cells of a human immunodeficiency virus (HIV)-1-infected mother protect the fetus from HIV-1 infection is unclear. Interferons (IFNs) inhibit the replication of viruses by acting at various stages of the life cycle and may play a role in protecting against vertical transmission of HIV-1. In addition the β-chemokines RANTES (regulated on activation T cell expressed and secreted), macrophage inflammatory protein-1-α (MIP-1α), and MIP-1β can block HIV-1 entry into cells by preventing the binding of the macrophage-trophic HIV-1 strains to the coreceptorCCR5. In this study the production of IFNs and β-chemokines by placental trophoblasts of HIV-1-infected women who were HIV-1 non-transmitters was examined. Methods: Placental trophoblastic cells were isolated from 29 HIV-1-infected and 10 control subjects. Supernatants of trophoblast cultures were tested for the production of IFNs and β-chemokines by enzyme linked immunosorbent assay (ELISA). Additionally, HIV-1-gag and IFN-β transcripts were determined by a semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) assay. Results: All placental trophoblasts of HIV-1-infected women contained HIV-1-gag transcripts. There were no statistical differences in the median constitutive levels of IFN-α and IFN-γ produced by trophoblasts of HIV-1- infected and control subjects. In contrast, trophoblasts of HIV-1-infected women constitutively produced significantly higher levels of IFN-β protein than trophoblasts of control subjects. Furthermore, the median levels of β-chemokines produced by trophoblasts of HIV-infected and control women were similar. Conclusions: Since there was no correlation between the placental HIV load and the production of interferons or β-chemokines, the role of trophoblast-derived IFNs and β-chemokines in protecting the fetus from infection with HIV-1 is not clear.