Cytomegalovirus and the role of interferon in the expression of tumor necrosis factor-related apoptosis-inducing ligand in the placenta

Objective: Cytomegalovirus infection causes adverse outcomes during pregnancy. Our objective was to determine the role of cytomegalovirus in modulating tumor necrosis factor (TNF)-related apoptosis-inducing ligand expression in the placenta. Study Design: TNF-related apoptosis-inducing ligand messenger RNA and protein were quantified in cytomegalovirus-infected placental fibroblasts by polymerase chain reaction and enzyme-linked immunosorbent assays, respectively. Blocking antibodies against interferon and type I interferon receptor were applied to culture medium to characterize the role of type I interferon in cytomegalovirus-induced TNF-related apoptosis-inducing ligand upregulation. Results: Expression of TNF-related apoptosis-inducing ligand messenger RNA and protein was increased in cytomegalovirus-infected placental fibroblasts, compared with uninfected controls. The cytomegalovirus-induced TNF-related apoptosis-inducing ligand messenger RNA upregulation was demonstrated across gestation, occurred in the absence of viral gene expression, and required cellular protein synthesis. TNF-related apoptosis-inducing ligand messenger RNA upregulation was markedly attenuated by inactivation of either type I interferon or its receptor. Conclusion: One mechanism by which cytomegalovirus infection causes unfavorable pregnancy outcomes may involve placental upregulation of TNF-related apoptosis-inducing ligand via an interferon-mediated pathway.