Zika virus infection of pregnant Ifnar1^−/− mice triggers strain-specific differences in fetal outcomes

Abstract

Zika virus (ZIKV) is a flavivirus that causes a constellation of adverse fetal outcomes collectively termed Congenital Zika Syndrome (CZS). However, not all pregnancies exposed to ZIKV result in an infant with apparent defects. During the 2015-2016 American outbreak of ZIKV, CZS rates varied by geographic location. The underlying mechanisms responsible for this heterogeneity in outcomes have not been well defined. Therefore, we sought to characterize and compare the pathogenic potential of multiple Asian/American-lineage ZIKV strains in an established Ifnar1 pregnant mouse model. Here, we show significant differences in the rate of fetal demise following maternal inoculation with ZIKV strains from Puerto Rico, Panama, Mexico, Brazil, and Cambodia. Rates of fetal demise broadly correlated with maternal viremia but were independent of fetus and placenta virus titer, indicating that additional underlying factors contribute to fetus outcome. Our results, in concert with those from other studies, suggest that subtle differences in ZIKV strains may have important phenotypic impacts. With ZIKV now endemic in the Americas, greater emphasis needs to be placed on elucidating and understanding the underlying mechanisms that contribute to fetal outcome.

Congenital Rift Valley fever in Sprague Dawley rats is associated with diffuse infection and pathology of the placenta

“…There was surprisingly little inflammation in any placental structure. Zika virus (ZIKV) infection of pregnant IFNAR1 knockout mice via footpad injection can result in vertical transmission involving severe necrosis of the decidua and basal zone (Bohm et al, 2021; Jaeger et al, 2019); however, decidual necrosis in ZIKV-infected rodents and pregnant women (Rabelo et al, 2020) is not associated with adverse fetal outcomes such as death or microcephaly. Vertical transmission of human immunodeficiency virus in placentas from 1 st and 2 nd trimester abortions is also correlated with necrosis of the decidua (Jauniaux et al, 1988).…”