| Abstrakt: |
Zika virus (ZIKV) is a mosquito-borne flavivirus that can vertically transmit from mother to fetus, potentially causing congenital defects, including microcephaly. It is not fully understood why some fetuses experience severe complications after in utero exposure to ZIKV, whereas others do not. Given the antigenic similarity between ZIKV and the closely related virus dengue (DENV) and the potential of DENV-specific antibodies to enhance ZIKV disease severity in mice, we questioned whether maternal DENV immunity could influence fetal outcomes in a nonhuman primate model of ZIKV vertical transmission. We found significantly increased severity of congenital Zika syndrome (CZS) in fetuses of DENV-immune cynomolgus macaques infected with ZIKV in early pregnancy compared with naïve controls, which occurred despite no effect on maternal ZIKV infection or antibody responses. Ultrasound measurements of head circumference and biparietal diameter measurements taken sequentially throughout pregnancy demonstrated CZS in fetuses of DENV-immune pregnant macaques. Furthermore, severe CZS enhanced by DENV immunity was typified by reduced cortical thickness and increased frequency of neuronal death, hemorrhaging, cellular infiltrations, calcifications, and lissencephaly in fetal brains. This study shows that maternal immunity to DENV can worsen ZIKV neurological outcomes in fetal primates, and it provides an animal model of vertical transmission closely approximating human developmental timelines that could be used to investigate severe ZIKV disease outcomes and interventions in fetuses. Editor's summary: Pregnant women infected with Zika virus (ZIKV) can vertically transmit virus to fetuses, which has been linked to congenital ZIKV syndrome. Understanding how ZIKV infection affects prenatal and neonatal development is critical for human health. Here, Saron et al. and Moadab et al. used cynomolgus and rhesus macaque models, respectively, to understand how maternal ZIKV infection influences fetal development. Saron et al. found that preexisting immunity to dengue virus, a related flavivirus, worsened severity of CZS. Moadab et al. found that maternal ZIKV infection alone was sufficient to reduce infant size and affect social behaviors. Together, these papers shed light on the impacts of ZIKV infection on fetal and early life development. —Christiana Fogg and Courtney Malo [ABSTRACT FROM AUTHOR] |
