A rhesus macaque model of congenital cytomegalovirus infection reveals a spectrum of vertical transmission outcomes.

Overview

Congenital cytomegalovirus (cCMV) is the leading infectious cause of birth defects worldwide, yet immune determinants of protection to inform maternal vaccine design remain elusive due to the lack of a translational animal model. Here, we characterized the outcome of primary rhesus CMV (RhCMV) infection in pregnant, immunocompetent, RhCMV-naïve rhesus macaques. RhCMV DNA was detected in amniotic fluid and/or fetal tissues in six of 12 (50% placental transmission) dams following early second trimester gestation RhCMV inoculation. Widespread tissue dissemination dominated by one of two inoculated RhCMV strains was present in one fetus (8.3% cCMV disease). RhCMV DNA detection in the amniotic fluid was associated with elevated fetal and maternal plasma TNF-alpha and reduced maternal brain-derived neurotrophic factor and IL-10 levels. Maternal RhCMV exposure during pregnancy had a broad impact on the placenta and fetus even in the absence of congenital infection, as evidenced by ubiquitous maternal-fetal interface infection, and reduced placental efficiency and small-for-gestation age fetuses compared to control pregnancies. This model provides new insights into the complexity of CMV vertical transmission and can be used to evaluate immune and viral determinants of protection against cCMV.