1. A clinical and histopathological study of malformations observed in fetuses infected by the Zika virus
- Author
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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), and Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP]
- 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 - 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.
- Published
- 2018