Article (Scientific journals)
Activation of Interferon-Stimulated Genes following Varicella-Zoster Virus Infection in a Human iPSC-Derived Neuronal In Vitro Model Depends on Exogenous Interferon-α.
Boeren, Marlies; Van Breedam, Elise; Buyle-Huybrecht, Tamariche et al.
2022In Viruses, 14 (11), p. 2517
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Keywords :
antiviral response; axonal infection; iPSC; innate immune response; interferon-stimulated genes; interferon-α; neuronal models; neurons; varicella-zoster virus; Interferon-alpha; Humans; Herpesvirus 3, Human/physiology; Cells, Cultured; Chickenpox; Herpes Zoster; Induced Pluripotent Stem Cells/virology; Interferon-alpha/immunology; Neurons/virology; Virology; Infectious Diseases
Abstract :
[en] Varicella-zoster virus (VZV) infection of neuronal cells and the activation of cell-intrinsic antiviral responses upon infection are still poorly understood mainly due to the scarcity of suitable human in vitro models that are available to study VZV. We developed a compartmentalized human-induced pluripotent stem cell (hiPSC)-derived neuronal culture model that allows axonal VZV infection of the neurons, thereby mimicking the natural route of infection. Using this model, we showed that hiPSC-neurons do not mount an effective interferon-mediated antiviral response following VZV infection. Indeed, in contrast to infection with Sendai virus, VZV infection of the hiPSC-neurons does not result in the upregulation of interferon-stimulated genes (ISGs) that have direct antiviral functions. Furthermore, the hiPSC-neurons do not produce interferon-α (IFNα), a major cytokine that is involved in the innate antiviral response, even upon its stimulation with strong synthetic inducers. In contrast, we showed that exogenous IFNα effectively limits VZV spread in the neuronal cell body compartment and demonstrated that ISGs are efficiently upregulated in these VZV-infected neuronal cultures that are treated with IFNα. Thus, whereas the cultured hiPSC neurons seem to be poor IFNα producers, they are good IFNα responders. This could suggest an important role for other cells such as satellite glial cells or macrophages to produce IFNα for VZV infection control.
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Boeren, Marlies;  Laboratory of Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, 2610 Antwerp, Belgium ; Laboratory of Experimental Hematology (LEH), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, 2610 Antwerp, Belgium ; Antwerp Center for Translational Immunology and Virology (ACTIV), Vaccine and Infectious Disease Institute, University of Antwerp, 2610 Antwerp, Belgium
Van Breedam, Elise ;  Laboratory of Experimental Hematology (LEH), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, 2610 Antwerp, Belgium
Buyle-Huybrecht, Tamariche;  Laboratory of Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, 2610 Antwerp, Belgium ; Laboratory of Experimental Hematology (LEH), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, 2610 Antwerp, Belgium ; Antwerp Center for Translational Immunology and Virology (ACTIV), Vaccine and Infectious Disease Institute, University of Antwerp, 2610 Antwerp, Belgium
Lebrun, Marielle  ;  Université de Liège - ULiège > Département des sciences de la vie > Virologie - Immunologie
Meysman, Pieter ;  Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing (AUDACIS), 2610 Antwerp, Belgium ; Adrem Data Lab, Department of Computer Science, University of Antwerp, 2610 Antwerp, Belgium ; Biomedical Informatics Research Network Antwerp (Biomina), University of Antwerp, 2610 Antwerp, Belgium
Sadzot, Catherine ;  Université de Liège - ULiège > Département des sciences de la vie
Van Tendeloo, Viggo F ;  Laboratory of Experimental Hematology (LEH), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, 2610 Antwerp, Belgium
Mortier, Geert;  Department of Medical Genetics, Antwerp University Hospital, University of Antwerp, 2610 Antwerp, Belgium
Laukens, Kris ;  Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing (AUDACIS), 2610 Antwerp, Belgium ; Adrem Data Lab, Department of Computer Science, University of Antwerp, 2610 Antwerp, Belgium ; Biomedical Informatics Research Network Antwerp (Biomina), University of Antwerp, 2610 Antwerp, Belgium
Ogunjimi, Benson;  Antwerp Center for Translational Immunology and Virology (ACTIV), Vaccine and Infectious Disease Institute, University of Antwerp, 2610 Antwerp, Belgium ; Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing (AUDACIS), 2610 Antwerp, Belgium ; Centre for Health Economics Research & Modelling Infectious Diseases (CHERMID), Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, 2610 Antwerp, Belgium ; Department of Paediatrics, Antwerp University Hospital, 2610 Antwerp, Belgium
Ponsaerts, Peter ;  Laboratory of Experimental Hematology (LEH), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, 2610 Antwerp, Belgium
Delputte, Peter ;  Laboratory of Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, 2610 Antwerp, Belgium ; Infla-Med, University of Antwerp, 2610 Antwerp, Belgium
Language :
English
Title :
Activation of Interferon-Stimulated Genes following Varicella-Zoster Virus Infection in a Human iPSC-Derived Neuronal In Vitro Model Depends on Exogenous Interferon-α.
Publication date :
14 November 2022
Journal title :
Viruses
eISSN :
1999-4915
Publisher :
MDPI AG, Switzerland
Volume :
14
Issue :
11
Pages :
2517
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
FWO - Fonds Wetenschappelijk Onderzoek Vlaanderen [BE]
UA - University of Antwerp [BE]
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since 15 February 2023

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