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Human three-dimensional engineered neural tissue reveals cellular and molecular events following cytomegalovirus infection.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Cosset Érika, Martinez Yannick, Preynat-Seauve Olivier, Lobrinus Johannes-Alexander, Tapparel Caroline, Cordey Samuel, Peterson Hedi, Petty Tom J, Colaianna Marilena, Tieng Vannary, Tirefort Diderik, Dinnyes Andras, Dubois-Dauphin Michel, Kaiser Laurent, Krause Karl-Heinz, Cosset Érika, Martinez Yannick, Preynat-Seauve Olivier, Lobrinus Johannes-Alexander, Tapparel Caroline, Cordey Samuel, Peterson Hedi, Petty Tom J, Colaianna Marilena, Tieng Vannary, Tirefort Diderik, Dinnyes Andras, Dubois-Dauphin Michel, Kaiser Laurent, Krause Karl-Heinz,
Project Rhinovirus et entérovirus: déterminants génomiques et phénotypes associés
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Original article (peer-reviewed)

Journal Biomaterials
Volume (Issue) 53
Page(s) 296 - 308
Title of proceedings Biomaterials
DOI 10.1016/j.biomaterials.2015.02.094

Open Access

Abstract

Human cytomegalovirus (HCMV) is the most common cause of congenital infection of the central nervous system (CNS). To overcome the limited access to human neural tissue and stringent species specificity of HCMV, we used engineered neural tissues to: (i) provide a technical advance to mimick features of HCMV infection in a human neural fetal tissue in vitro and (ii) characterize the molecular and cellular phenomenon following HCMV infection in this tissue. Herein, we infected hESC-derived engineered neural tissues (ENTs) whose organization resembles fetal brain. Transcriptome analysis of ENTs demonstrated that HCMV infection displayed features of the infection with the expression of genes involved in lipid metabolism, growth and development, as well as stress and host-response in a time-dependent manner. Immunohistochemical analysis demonstrated that HCMV did not firstly infect neural tubes (i.e. radially organized, proliferating stem cell niches), but rather an adjacent side population of post-mitotic cells expressing nestin, doublecortin, Sox1, musashi and vimentin markers. Importantly, we observe the same tropism in naturally HCMV-infected fetal brain specimens. To the best of our knowledge this system represents the first human brain-like tissue able to provide a more physiologically model for studying HCMV infection.
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