Nonhuman primate model mirroring human congenital cytomegalovirus infection reveals a spectrum of vertical transmission outcomes

TL;DR

A new nonhuman primate model of cytomegalovirus infection during pregnancy reveals how the virus can be passed to the fetus and affects both mother and baby.

Contribution

The study introduces a translational nonhuman primate model that mirrors human congenital CMV infection and vertical transmission dynamics.

Findings

RhCMV was transmitted to 50% of fetuses, with one case of full-blown fetal disease.

CMV exposure during pregnancy caused placental and fetal changes even without congenital infection.

Immune markers like TNF-alpha were elevated in transmitted cases, while IL-10 and BDNF were reduced.

Abstract

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, CMV-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). Placental transmission was associated with elevated fetal and maternal plasma TNF-alpha and reduced maternal brain-derived neurotrophic factor and IL-10 levels. CMV 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 recapitulates key aspects of human cCMV and provides new insights into the complexity of CMV vertical transmission.

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