Zika Virus Infection at Different Pregnancy Stages: Anatomopathological Findings, Target Cells and Viral Persistence in Placental Tissues.

Lucia De Noronha,Iolanda Maria Novadzki,Andreia Akemi Suzukawa,Laurina Setsuko Tanabe,Claudia Nunes Duarte Dos Santos,Marina Azevedo,Marion Burger,Mayra Marinho Presibella,Patricia Z Rebutini,Camila Zanluca

doi:10.3389/fmicb.2018.02266

Abstract

Zika virus (ZIKV) infection in humans has been associated with congenital malformations and other neurological disorders, such as Guillain-Barré syndrome. The mechanism(s) of ZIKV intrauterine transmission, the cell types involved, the most vulnerable period of pregnancy for severe outcomes from infection and other physiopathological aspects are not completely elucidated. In this study, we analyzed placental samples obtained at the time of delivery from a group of 24 women diagnosed with ZIKV infection during the first, second or third trimesters of pregnancy. Villous immaturity was the main histological finding in the placental tissues, although placentas without alterations were also frequently observed. Significant enhancement of the number of syncytial sprouts was observed in the placentas of women infected during the third trimester, indicating the development of placental abnormalities after ZIKV infection. Hyperplasia of Hofbauer cells (HCs) was also observed in these third-trimester placental tissues, and remarkably, HCs were the only ZIKV-positive fetal cells found in the placentas studied that persisted until birth, as revealed by immunohistochemical (IHC) analysis. Thirty-three percent of women infected during pregnancy delivered infants with congenital abnormalities, although no pattern correlating the gestational stage at infection, the IHC positivity of HCs in placental tissues and the presence of congenital malformations at birth was observed. Placental tissue analysis enabled us to confirm maternal ZIKV infection in cases where serum from the acute infection phase was not available, which reinforces the importance of this technique in identifying possible causal factors of birth defects. The results we observed in the samples from naturally infected pregnant women may contribute to the understanding of some aspects of the pathophysiology of ZIKV.

Highlights

Zika virus (ZIKV) is an emergent arthropod-borne virus that belongs to the genus Flavivirus of the Flaviviridae family [International Comittee on Taxonomy of Viruses (ICTV), 2017]
Neither ZIKV RNA nor anti-ZIKV IgM were detected in samples of amniotic fluid, newborn cerebrospinal fluid (CSF) or ocular/oral swabs in the cases described in this article
Of the five newborn serum samples available, one presented anti-ZIKV IgM, indicating transplacental infection, no congenital disorder was observed at the time of delivery in this case (Table 1, case LRV/16 1065)

Summary

Introduction

Zika virus (ZIKV) is an emergent arthropod-borne virus that belongs to the genus Flavivirus of the Flaviviridae family [International Comittee on Taxonomy of Viruses (ICTV), 2017]. This virus is primarily transmitted through the bite of the Aedes mosquito (Zanluca and Duarte dos Santos, 2016). Cases of neurological manifestations, such as Guillain-Barré syndrome (Beckham et al, 2016; Noronha et al, 2016; Schuler-Faccini et al, 2016), have been reported in patients diagnosed with ZIKV. By March 17, 2017, thirtyone countries or territories in the Americas had reported central nervous system malformations that were potentially associated with ZIKV infection, and Brazil is the most affected country to date [World Health Organization (WHO), 2017]

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