# 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.

## Key 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.