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

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...

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Bibliographic Details
Published in:Biomaterials 2015-06, Vol.53, p.296-308
Main Authors: 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
Format: Article
Language:English
Subjects:
Advanced Basic Science
Brain
Cell Line
Cellular
Central nervous system
Cytomegalovirus Infections - metabolism
Dentistry
Gene expression
Human
Human cytomegalovirus
Humans
Infection
Nerve tissue engineering
Nervous System - embryology
Nervous System - virology
Neural cell
Stem cell
Surgical implants
Three dimensional
Tissue Engineering
Tropism
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Summary: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.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2015.02.094