Abstract

In 2015 Zika virus (ZIKV) emerged for the first time in South America. The following ZIKV epidemic resulted in the appearance of a clinical phenotype with microcephaly and other severe malformations in newborns. So far, mechanisms of ZIKV induced damage to the fetus are not completely understood. Previous data suggest that ZIKV may bypass the placenta to reach the fetus. Thus, animal models for ZIKV infection are important to facilitate studies about ZIKV infection during pregnancy. Here, we used ultrasound based imaging (USI) to characterize ZIKV induced pathogenesis in the pregnant Type I interferon receptor-deficient (IFNAR-/-) mouse model. Based on USI we suggest the placenta to be a primary target organ of ZIKV infection enabling ZIKV spreading to the fetus. Moreover, in addition to direct infection of the fetus, the placental ZIKV infection may cause an indirect damage to the fetus through reduced uteroplacental perfusion leading to intrauterine growth retardation (IUGR) and fetal complications as early as embryonic day (ED) 12.5. Our data confirmed the capability of USI to characterize ZIKV induced modifications in mouse fetuses. Data from further studies using USI to monitor ZIKV infections will contribute to a better understanding of ZIKV infection in pregnant IFNAR-/- mice.

Highlights

  • Zika virus (ZIKV) has been first identified in 1947 in a sentinel monkey in ZIKV forest in Africa

  • To confirm pregnancy after positive plug-check, mice were examined on estimated embryonic day (ED) 4.5 by ultrasound imaging (USI)

  • ZIKV infection during pregnancy has been confirmed to lead to severe congenital malformations Discussiondeath in human fetuses

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Summary

Introduction

ZIKV has been first identified in 1947 in a sentinel monkey in ZIKV forest in Africa. Sporadic ZIKV outbreaks have occurred in Africa and. Another clinical outcome of ZIKV infection is the induction of the Guillain-Barré syndrome manifesting in various neurological disorders through damaging the peripheral nervous system [3,4,5,6]. Recent data confirmed that ZIKV can be spread through the sexual and vertical route [10,11,12,13] In 2015 the virus suddenly emerged on the American continent causing an epidemic of congenital human abnormalities. ZIKV infection during pregnancy resulted in fetal abnormalities such as microcephaly, neurological malfunction, and spontaneous abortion [11,14,15].

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