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.


METHODS
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.


CONCLUSIONS
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.
Andrews
Janet I
JI
Department of Obstetrics and Gynecology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
Griffith
Thomas S
TS
Meier
Jeffery L
JL
D003586:Cytomegalovirus Infections / Q000276:immunology*; D005260:Female; D006801:Humans; D007372:Interferons / Q000276:immunology*; D010920:Placenta / Q000276:immunology*; D011247:Pregnancy; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000096:biosynthesis*; D015854:Up-Regulation; D014779:Virus Replication / Q000276:immunology
D053221:TNF-Related Apoptosis-Inducing Ligand; D007372:Interferons