Significance Current evidence indicates that primary human cytomegalovirus infection early in gestation increases the likelihood of fetal/neonatal disease. Our studies with rhesus monkeys have demonstrated that the developing macaque brain is sensitive to rhesus CMV (RhCMV) infection, and that direct infection results in pathologic outcomes comparable to those observed in humans congenitally infected with human CMV. Objectives The objectives include (1) to characterize the developmental and neurologic sequelae in rhesus fetuses/neonates infected with RhCMV at different stages of gestation and relate these findings to protective maternal antiviral antibody responses to prevent damaging CMV infection; (2) to define the kinetics of IgG placental transport by quantifying titers of maternal and fetal anti-RhCMV antibodies in relation to gestational age; and (3) to determine early viral replication parameters in relation to timing of fetal infection and maternal/fetal antiviral antibody titers. Results Monkey fetuses of RhCMV seropositive dams were directly inoculated intraperitoneal with RhCMV strain 68-1 on gestational day (GD) 50 or 65 and compared to controls. Six of 12 GD 50-inoculated fetuses were terminated due to impending demise; two were sonographically identified with diaphragmatic defects incompatible with life. Of the 12 infected fetuses that survived to term, two were identified in utero with hydrocephalus, and one with intrauterine growth restriction (IUGR). A series of neurobehavioral/neurologic tests were conducted postnatally (through 1 month postnatal age), including auditory brainstem responses (ABR). Results of the ABR suggested deficits in auditory function for some RhCMV-inoculated infants, although additional data for a more extended period will be required in order to achieve statistical significance. Neuropathologic analyses indicated nuclear and cytoplasmic inclusions, lymphocytosis, gliosis, cystic changes, and/or calcification for CMV-infec ted fetuses/neonates. All neurodegenerative changes were confined to the leptomeninges, white matter, and ventricles. Future Directions Studies will continue to focus on the postnatal complications of prenatal infection, and characterization of the specificity of RhCMV proteins and epitopes eliciting host antiviral immune responses. KEY WORDS cytomegalovirus, fetus, growth, neuropathology FUNDING NIH Grant NS36859 PUBLICATIONS Tarantal, A.F., Salamat, S.M., Britt, W.J., Luciw, P.A., Hendrickx, A.G., Barry, P.A. Neuropathogenesis induced by rhesus cytomegalovirus in fetal rhesus monkeys (Macaca mulatta). J. Infect. Dis. 177:446-450, 1998.
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