BioProject

Cytomegalovirus (CMV) is the most common congenital infection worldwide, causing deafness and neurodevelopmental delay in infected infants. More...

Cytomegalovirus (CMV) is the most common congenital infection worldwide, causing deafness and neurodevelopmental delay in infected infants. Preexisting maternal immunity to CMV is known to influence the incidence and severity of congenital infection. To establish the role of maternal antibody in protection against placental CMV transmission, 6 rhesus CMV (RhCMV)-seronegative rhesus monkey dams were CD4+ T cell depleted at the end of the first trimester of pregnancy and treated with either a single dose of standardly-produced hyperimmune globulin (HIG) (n=3) or a dose-optimized regimen of a potently-neutralizing HIG (n=3) prior to IV inoculation with a mixture of RhCMV strains. Passive infusion with HIG provided complete protection against fetal loss (0/6 HIG-treated vs. 5/6 control dams aborted; p=0.015). Furthermore, the dose-optimized, highly-neutralizing HIG product reduced the magnitude and diversity of maternal plasma RhCMV populations and inhibited placental transmission of RhCMV (0/3 transmitted), suggesting that pre-existing highly-neutralizing antibodies are sufficient to prevent congenital CMV infection and disease. In this study, we sought to investigate the placental transcriptome to determine whether: a) RhCMV congenital infection was being controlled at the level of the placenta, b) what genes are up-regulated following RhCMV congenital infection, and c) whether there are any genes associated with protection against viral infection. Overall design: This study contains 3 groups of monkeys: control, standard HIG-infused, and high-potency HIG-infused. All control animals + 2/3 standard HIG-infused animals had congenitally infected fetuses. Thus, there are 4 independent groups: (1) control + CMV-infected, (2) standard + CMV-infected, (3) standard + not CMV-infected, and (4) high-potency HIG + not CMV-infected. RNA was extracted from sections of fetal placenta for 7 animals in total. Less...