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      Placental Inflammation and Fetal Injury in a Rare Zika Case Associated With Guillain-Barré Syndrome and Abortion

      case-report

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          Abstract

          Zika virus (ZIKV) is an emerging virus involved in recent outbreaks in Brazil. The association between the virus and Guillain-Barré syndrome (GBS) or congenital disorders has raised a worldwide concern. In this work, we investigated a rare Zika case, which was associated with GBS and spontaneous retained abortion. Using specific anti-ZIKV staining, the virus was identified in placenta (mainly in Hofbauer cells) and in several fetal tissues, such as brain, lungs, kidneys, skin and liver. Histological analyses of the placenta and fetal organs revealed different types of tissue abnormalities, which included inflammation, hemorrhage, edema and necrosis in placenta, as well as tissue disorganization in the fetus. Increased cellularity (Hofbauer cells and TCD8 + lymphocytes), expression of local pro-inflammatory cytokines such as IFN-γ and TNF-α, and other markers, such as RANTES/CCL5 and VEGFR2, supported placental inflammation and dysfunction. The commitment of the maternal-fetal link in association with fetal damage gave rise to a discussion regarding the influence of the maternal immunity toward the fetal development. Findings presented in this work may help understanding the ZIKV immunopathogenesis under the rare contexts of spontaneous abortions in association with GBS.

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          Most cited references26

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          Immunity to homologous grafted skin; the fate of skin homografts transplanted to the brain, to subcutaneous tissue, and to the anterior chamber of the eye.

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            Vaginal Exposure to Zika Virus during Pregnancy Leads to Fetal Brain Infection.

            Zika virus (ZIKV) can be transmitted sexually between humans. However, it is unknown whether ZIKV replicates in the vagina and impacts the unborn fetus. Here, we establish a mouse model of vaginal ZIKV infection and demonstrate that, unlike other routes, ZIKV replicates within the genital mucosa even in wild-type (WT) mice. Mice lacking RNA sensors or transcription factors IRF3 and IRF7 resulted in higher levels of local viral replication. Furthermore, mice lacking the type I interferon (IFN) receptor (IFNAR) became viremic and died of infection after a high-dose vaginal ZIKV challenge. Notably, vaginal infection of pregnant dams during early pregnancy led to fetal growth restriction and infection of the fetal brain in WT mice. This was exacerbated in mice deficient in IFN pathways, leading to abortion. Our study highlights the vaginal tract as a highly susceptible site of ZIKV replication and illustrates the dire disease consequences during pregnancy.
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              The role of inflammation and infection in preterm birth.

              Inflammation has been implicated in the mechanisms responsible for preterm and term parturition, as well as fetal injury. Out of all of the suspected causes of preterm labor and delivery, infection and/or inflammation is the only pathological process for which both a firm causal link with preterm birth has been established and a molecular pathophysiology defined. Inflammation has also been implicated in the mechanism of spontaneous parturition at term. Most cases of histopathological inflammation and histological chorioamnionitis, both in preterm and term labor, are sub-clinical in nature. The isolation of bacteria in the amniotic fluid, known as microbial invasion of the amniotic cavity, is a pathological finding; the frequency of which is dependent upon the clinical presentation and gestational age. This article reviews the role of inflammation in preterm and term parturition.
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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                16 May 2018
                2018
                : 9
                : 1018
                Affiliations
                [1] 1Laboratório de Ultraestrutura e Biologia Tecidual, Universidade do Estado do Rio de Janeiro , Rio de Janeiro, Brazil
                [2] 2Faculdade de Medicina de Campos, Campos dos Goytacazes , Rio de Janeiro, Brazil
                [3] 3Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz , Rio de Janeiro, Brazil
                [4] 4Laboratório de Modelagem Molecular, Instituto de Química Orgânica, Universidade Federal do Rio de Janeiro , Rio de Janeiro, Brazil
                [5] 5Anatomia Patológica, Hospital Municipal Jesus , Rio de Janeiro, Brazil
                [6] 6Anatomia Patológica, Universidade Federal do Estado do Rio de Janeiro , Rio de Janeiro, Brazil
                Author notes

                Edited by: Juarez Antonio Simões Quaresma, Instituto Evandro Chagas, Brazil

                Reviewed by: Kuldeep Dhama, Indian Veterinary Research Institute (IVRI), India; Yan Li, Agency for Science, Technology and Research (A*STAR), Singapore; Jan Muench, Universität Ulm, Germany; Guido Poli, Vita-Salute San Raffaele University, Italy

                *Correspondence: Marciano V. Paes marciano@ 123456ioc.fiocruz.br

                This article was submitted to Microbial Immunology, a section of the journal Frontiers in Microbiology

                †These authors have contributed equally to this work.

                Article
                10.3389/fmicb.2018.01018
                5964188
                29867903
                dc62dfe2-077e-40fb-a7c8-0b66ad9fd22d
                Copyright © 2018 Rabelo, Souza, Salomão, Oliveira, Sentinelli, Lacerda, Saraquino, Rosman, Basílio-de-Oliveira, Carvalho and Paes.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 26 February 2018
                : 30 April 2018
                Page count
                Figures: 4, Tables: 0, Equations: 0, References: 44, Pages: 10, Words: 5883
                Funding
                Funded by: Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro 10.13039/501100004586
                Award ID: E-26/010.001.498/2016
                Award ID: E-26/110.511/2014
                Categories
                Microbiology
                Case Report

                Microbiology & Virology
                zika virus,immune response,guillain-barré syndrome,fetal infection,histopathology

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