Zika virus infection at mid-gestation results in fetal cerebral cortical injury and fetal death in the olive baboon

Abstract

Zika virus (ZIKV) infection during pregnancy in humans is associated with an increased incidence of congenital anomalies including microcephaly as well as fetal death and miscarriage and collectively has been referred to a Congenital Zika Syndrome (CZS).Animal models for ZIKV infection in pregnancy have been developed including mice and macaques. While microcephaly has been achieved in mice via direct injection of ZIKV into the fetal brain or via interference with interferon signaling, in macaques the primary fetal CZS outcome are ocular defects. In the present study we develope the olive baboon (Papio anubis), as a model for the vertical transfer of ZIKV during pregnancy. We infected four mid-gestation, timed-pregnant baboons with the French Polynesian ZIKV isolate (10 4 ffu) and examined the acute phase of vertical transfer by stopping the study of one dam at 7 days post infection (dpi), two at 14 dpi and one at 21 dpi. All dams exhibited mild to moderate rash and conjunctivitis; three of four dams exhibited viremia at 7 dpi. Of the three dams studied to 14 to 21 days, only one still exhibited viremia on day 14. Vertical transfer of ZIKV to the fetus was found in two pregnancies; in one, vertical transfer was associated with fetal death at ~14 dpi. In the other, vertical transfer was observed at 21 dpi.Both fetuses had ZIKV RNA in the fetal cerebral cortex as well as other tissues. The 21 dpi fetal cerebral cortex exhibited notable defects in radial glia, radial glial fibers, loss and or damage of immature oligodendrocytes and a loss in neuroprogenitor cells (NPCs). In addition, indices of pronounced neuroinflammation were observed including astrogliosis, increased microglia and IL-6 expression. The dams studied to 14 dpi (n=2) and 21 dpi (n=1) exhibited a anti-ZIKV IgM response and IgG response (21 dpi) that included transfer of the IgG to the fetal compartment (cord blood). The severity of systemic inflammatory

Oligodendrocytes are susceptible to Zika virus infection in a mouse model of perinatal exposure: Implications for CNS complications

“…Non‐human primate studies have also provided support for myelin involvement in the pathogenesis of ZIKV infection of the CNS. Oligodendroglial development was impaired in fetuses of mid‐gestation olive baboons infected systemically with a French Polynesian ZIKV isolate (H/PF/2013; Gurung et al, 2019) and white matter hypoplasia were reported in preterm pigtail macaque following systemic infection of the pregnant dam with a Cambodian isolate (FSS13025; Adams Waldorf et al, 2016). As in the current study, these non‐human primates were killed before the long‐term consequences were known and it will be important for future studies to address later outcomes, within the limitations of animal welfare issues.…”