Spondweni virus causes fetal harm in Ifnar1 mice and is transmitted by Aedes aegypti mosquitoes

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

“…In contrast, ZIKV-PR replicated to high titers in the placenta that corresponded to severe histopathology but did not result in fetal demise. No strain resulted in detectable fetal infection, which is different from what we have reported previously with African-lineage ZIKV (20, 21). However, the absence of ZIKV fetal infection does not preclude the possibility that pathology may develop later in pregnancy or even postnatally, similar to what has been observed in humans (33).…”

“…In contrast, ZIKV-inoculated dams displayed varying degrees of placental pathology, similar to what we have reported previously, with the most severe effects predominantly observed in the labyrinth zone, including necrosis, calcifications, thrombi, inflammation, and apoptosis (20, 21). Interestingly, the overall severity observed within virus groups was relatively subtle compared to our previous studies (20, 21), which may account for the higher background scores noted in the PBS control group ( Figure 2A-C ). There also were clear strain-specific differences in the amount of placental pathology observed, with ZIKV-CAM displaying the most severe histologic phenotype ( Figure 2 ).…”

“…Pregnant Ifnar1 −/− dams were inoculated with 1×10 3 PFU of ZIKV-PR, ZIKV-PAN, ZIKV-MEX, ZIKV-BRA, or ZIKV-CAM via subcutaneous footpad inoculation at embryonic day 7.5 (E7.5), corresponding to the mid-to-late first trimester in humans (27). Based on results from our past studies (20, 21), we chose this dose to minimize the potential confounding impacts of maternal illness on fetal outcomes. Maternal serum samples were collected at 2, 4, and 7 days post inoculation (dpi) to confirm infection and examine viremia kinetics ( Figure 1A ).…”

“…To characterize the range of pathogenic outcomes and assess the effect of ZIKV strain on in-utero 91 exposure, we utilized a well-established murine pregnancy model for ZIKV (20,21). Ifnar1 -/dams were 92 time-mated with wildtype (WT) males to produce fetuses and a maternal-fetal interface (MFI) with 93 intact interferon (IFN) signaling.…”

“…We therefore aimed to better understand heterogeneity in ZIKV-associated pregnancy outcomes by investigating whether there are Asian/American-lineage strain-specific phenotypic differences by using mice lacking type I interferon signaling (Ifnar1 -/-). Although there are limitations regarding the translational relevance of this model, transplacental ZIKV infection and fetal damage have been demonstrated (20)(21)(22)(23), and it has been used to compare maternal infection parameters, placental pathology, fetal infection, and outcomes between ZIKV strains and the closely-related Spondweni virus (20)(21)(22). Congenital ZIKV studies in pregnant mouse models have used a variety of virus strains, as well as timing, route, and dose of inoculation (22)(23)(24)(25).…”