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A clinical and histopathological study of malformations observed in fetuses infected by the Zika virus

Authors :
Marc Thiry
Christian Alfano
Férechté Encha-Razavi
Marine Driessen
Tania Attié-Bitach
Michel Vekemans
Marianne Leruez-Ville
Laurent Nguyen
Yves Ville
Thérèse Couderc
Marc Lecuit
Aurélie Beaufrère
Nicolas Thelen
Maryse Bonnière
Bettina Bessières
Laboratoire Histologie Embryologie Cytogénétique [CHU Necker]
CHU Necker - Enfants Malades [AP-HP]
Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Service de Gynécologie Obstétrique [CHU Necker]
GIGA-Neurosciences [Université Liège]
GIGA [Université Liège]
Université de Liège-Université de Liège
Biologie des Infections - Biology of Infection
Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Université Paris Descartes - Paris 5 (UPD5)
Centre d'infectiologie Necker-Pasteur [CHU Necker]
Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP]
Imagine - Institut des maladies génétiques (IMAGINE - U1163)
Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Laboratoire de Virologie [CHU Necker]
Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP]
Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
This project was funded in part by the European Union's Horizon 2020 Research and Innovation Program under ZIKAlliance Grant Agreement N° 734548 (to L.N. and M.L.) and by the LabEx IBEID, Institut Pasteur, and INSERM.
ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010)
European Project: 734548,ZIKAlliance(2016)
DIAKITE, andrée
Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID
A global alliance for Zika virus control and prevention - ZIKAlliance - 2016-10-01 - 2019-09-30 - 734548 - VALID
Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)
Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP]
Source :
Brain Pathology, Brain Pathology, 2019, 29 (1), pp.114-125. ⟨10.1111/bpa.12644⟩, Brain Pathology, Wiley, 2019, 29 (1), pp.114-125. ⟨10.1111/bpa.12644⟩, Brain Pathol
Publication Year :
2018
Publisher :
Wiley, 2018.

Abstract

International audience; Background: The recent outbreak of Zika virus (ZIKV) infection and the associated increased prevalence of microcephaly in Brazil underline the impact of viral infections on embryo-fetal development. The aim of the present study is to provide a detailed clinical and histopathological study of the fetal disruption caused by the ZIKV, with a special focus on the associated neuropathological findings. Methods: A detailed feto-placental examination, as well as neuropathological and neurobiological studies were performed on three fetuses collected after pregnancy termination between 22 and 25 weeks of gestation (WG), because brain malforma-tions associated with a maternal and fetal ZIKV infection was diagnosed. Results: In all three cases, the maternal infection occurred during the first trimester of pregnancy. A small head was observed on the ultrasound examination of the second trimester of pregnancy and led to the diagnosis of ZIKV fetopathy and pregnancy termination. The fetal histopathological examination was unremarkable on the viscera but showed on the testis an interstitial lymphocytic infiltrate. The placenta contained a Hofbauer cells hyperplasia with signs of inflammation. Neu-ropathological findings included a meningoencephalitis and an ex vacuo hydrocepha-lus. Immunohistochemical studies showed the presence of T lymphocytic and histiocytic meningitis associated with an abundant cerebral astroglial and macrophagic reaction. In situ hybridization demonstrated, abundant ZIKV particles within the cerebral parenchyma mainly in the ventricular/subventricular zone and in the cortical plate. In addition massive cells death and endoplasmic reticulum damage were present. Conclusion: The present study reports on the clinical and histopathological findings observed in three fetuses infected by the ZIKV. It emphasizes the severity of brain damages and the minimal visceral and placental changes observed upon ZIKV infection. This confirms the selective neurotropism of ZIKV. Finally, it allows us to describe the cascade of multifactorial developmental defects leading to microcephaly.

Subjects

Subjects :
0301 basic medicine
Microcephaly
Pathology
[SDV]Life Sciences [q-bio]
MESH: Brain/virology
Zika virus
MESH: Pregnancy
0302 clinical medicine
Pregnancy
[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases
microcephaly
Research Articles
[SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases
[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology
[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology
biology
Zika Virus Infection
General Neuroscience
MESH: Aborted Fetus/physiopathology
Brain
meningoencephalitis
Meningoencephalitis
3. Good health
Micrencephaly
[SDV] Life Sciences [q-bio]
fetus
MESH: Brain/pathology
[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology
Aborted Fetus
[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology
[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases
Female
ER stress
Meningitis
Brazil
Hydrocephalus
medicine.medical_specialty
MESH: Hydrocephalus/pathology
MESH: Microcephaly
Pathology and Forensic Medicine
ZIKV infection
03 medical and health sciences
MESH: Zika Virus Infection/pathology
medicine
Humans
[SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology
Fetus
MESH: Humans
business.industry
MESH: Fetus
Zika Virus
MESH: Zika Virus/pathogenicity
medicine.disease
biology.organism_classification
030104 developmental biology
Neurology (clinical)
MESH: Brazil
business
MESH: Female
micrencephaly
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
030217 neurology & neurosurgery

Details

ISSN :
17503639 and 10156305
Volume :
29
Database :
OpenAIRE
Journal :
Brain Pathology
Accession number :
edsair.doi.dedup.....bdc0a5eb8cd0e81435bf85cc57768903