Abstract

Zika virus (ZIKV) infection of pregnant women is associated with pathologic complications of fetal development. Here, we infect pregnant rhesus macaques (Macaca mulatta) with a minimally passaged ZIKV isolate from Rio de Janeiro, where a high rate of fetal development complications was observed. The infection of pregnant macaques with this virus results in maternal viremia, virus crossing into the amniotic fluid (AF), and in utero fetal deaths. We also treated three additional ZIKV-infected pregnant macaques with a cocktail of ZIKV-neutralizing human monoclonal antibodies (nmAbs) at peak viremia. While the nmAbs can be effective in clearing the virus from the maternal sera of treated monkeys, it is not sufficient to clear ZIKV from AF. Our report suggests that ZIKV from Brazil causes fetal demise in non-human primates (NHPs) without additional mutations or confounding co-factors. Treatment with a neutralizing anti-ZIKV nmAb cocktail is insufficient to fully stop vertical transmission.

Highlights

  • Zika virus (ZIKV) infection of pregnant women is associated with pathologic complications of fetal development

  • We show that the ZIKV Rio U-1/2016 strain, isolated from the urine of a pregnant woman living in a region with high incidence of congenital Zika syndrome (CZS), causes fetal demise in a nonhuman primates (NHPs) host

  • Our results indicate that ZIKV Rio U-1/2016 is sufficient for causing fetal demise in the rhesus NHP model of ZIKV-infection

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Summary

Introduction

Zika virus (ZIKV) infection of pregnant women is associated with pathologic complications of fetal development. We infect pregnant rhesus macaques (Macaca mulatta) with a minimally passaged ZIKV isolate from Rio de Janeiro, where a high rate of fetal development complications was observed. We treated three additional ZIKV-infected pregnant macaques with a cocktail of ZIKVneutralizing human monoclonal antibodies (nmAbs) at peak viremia. Mohr et al.[13] have reported fetal demise following ZIKV PRVABC59 infection in a rhesus macaque. This animal had a bacterial infection, and it remains unclear if ZIKV infection alone is sufficient to cause demise of the rhesus fetus

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