Transfusion-Transmitted Zika Virus Infection in Pregnant Mice Leads to Broad Tissue Tropism With Severe Placental Damage and Fetal Demise.

Wanbo Tai,Weili Bao,Lanying Du,Jiawei Chen,Beth Shaz,Denis Voronin,Karina Yazdanbakhsh,Shibo Jiang,Debra A Kessler

doi:10.3389/fmicb.2019.00029

Abstract

Zika virus (ZIKV) infection during pregnancy can cause significant problems, particularly congenital Zika syndrome. Nevertheless, the potential deleterious consequences and associated mechanisms of transfusion-transmitted ZIKV infection on pregnant individuals and their fetuses and babies have not been investigated. Here we examined transmissibility of ZIKV through blood transfusion in ZIKV-susceptible pregnant A129 mice. Our data showed that transfused-transmitted ZIKV at the early infection stage led to significant viremia and broad tissue tropism in the pregnant recipient mice, which were not seen in those transfused with ZIKV-positive (ZIKV+) plasma at later infection stages. Importantly, pregnant mice transfused with early-stage, but not later stages, ZIKV+ plasma also exhibited severe placental infection with vascular damage and apoptosis, fetal infection and fetal damage, accompanied by fetal and pup death. Overall, this study suggests that transfusion-related transmission of ZIKV during initial stage of infection, which harbors high plasma viral titers, can cause serious adverse complications in the pregnant recipients and their fetuses and babies.

Highlights

Zika virus (ZIKV), a flavivirus in the Flaviviridae family, was first identified in rhesus monkeys in 1947 (Dick et al, 1952; Wikan and Smith, 2016)
We found that pregnant mice (E10–12) receiving plasma at the early-stage ZIKV infection containing a high titer (∼2.6 × 105 ± 5 × 104 PFU) of ZIKV exhibited severe ZIKV viremia, with significantly higher levels of ZIKV RNA (Figure 2A) and ZIKV titers (Figure 2B) than those receiving plasma containing a lower titer, early-stage ZIKV+
The data suggest that transfusion-transmitted ZIKV from early-stage infection can cause significant viremia, broad tissue tropism, and inflammation, with devastating effects during pregnancy, on the fetuses

Summary

Introduction

Zika virus (ZIKV), a flavivirus in the Flaviviridae family, was first identified in rhesus monkeys in 1947 (Dick et al, 1952; Wikan and Smith, 2016). Most people infected with ZIKV have no clinical symptoms or only exhibit mild symptoms, without requiring hospitalization. ZIKV infection during pregnancy can cause significant problems, congenital Zika syndrome, which involves congenital brain abnormalities, microcephaly at birth, and motor anomalies and epilepsy in infants, as well as other malformations. ZIKV infection is linked to Guillain-Barre syndrome (GBS), a severe neurological disease (Cao-Lormeau et al, 2016; Roze et al, 2017; Salinas et al, 2017; Simon et al, 2018). The association of ZIKV infection with these unexpected diseases has brought worldwide attention to study this virus and its pathogenic mechanisms

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