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Biomaterials. 2015;53:296-308. doi: 10.1016/j.biomaterials.2015.02.094. Epub 2015 Mar 17.

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

Author information

1
Laboratory of Immuno-hematology, Department of Genetic and Laboratory Medicine, Geneva University Hospital, University of Geneva, Geneva, Switzerland; Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
2
Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland; BioTalentum Ltd, Gödöllö 2100, Hungary.
3
Laboratory of Immuno-hematology, Department of Genetic and Laboratory Medicine, Geneva University Hospital, University of Geneva, Geneva, Switzerland.
4
Neuropathology Unit, Geneva University Hospital, Geneva, Switzerland.
5
Laboratory of Virology, Division of Infectious Diseases and Division of Laboratory Medicine, Geneva University Hospital, University of Geneva Medical School, Geneva, Switzerland.
6
Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
7
Department of Genetic Medicine and Development, University of Geneva Medical School, Swiss Institute of Bioinformatics, Geneva, Switzerland.
8
BioTalentum Ltd, Gödöllö 2100, Hungary; Molecular Animal Biotechnology Laboratory, Szent István University, Gödöllö 2100, Hungary.
9
Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland. Electronic address: Karl-Heinz.Krause@unige.ch.

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.

KEYWORDS:

Infection; Nerve tissue engineering; Neural cell; Stem cell

[Indexed for MEDLINE]

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