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Chikungunya virus infection induces ultrastructural changes and impaired neuronal differentiation of human neurospheres

Chikungunya virus (CHIKV) is an arthropod-borne virus recently associated with large outbreaks in many parts of the world. Infection is typically manifested as a febrile and self-limited illness, characterized by joint pain and myalgia, albeit severe neurological manifestations are also reported. Al...

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Autores principales: de Lima Cavalcanti, Thaíse Yasmine Vasconcelos, Azevedo, Elisa de Almeida Neves, Lima, Morganna Costa, Saraiva, Karina Lidiane Alcântara, Franca, Rafael Freitas Oliveira
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10213924/
https://www.ncbi.nlm.nih.gov/pubmed/37250062
http://dx.doi.org/10.3389/fmicb.2023.1152480
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author de Lima Cavalcanti, Thaíse Yasmine Vasconcelos
Azevedo, Elisa de Almeida Neves
Lima, Morganna Costa
Saraiva, Karina Lidiane Alcântara
Franca, Rafael Freitas Oliveira
author_facet de Lima Cavalcanti, Thaíse Yasmine Vasconcelos
Azevedo, Elisa de Almeida Neves
Lima, Morganna Costa
Saraiva, Karina Lidiane Alcântara
Franca, Rafael Freitas Oliveira
author_sort de Lima Cavalcanti, Thaíse Yasmine Vasconcelos
collection PubMed
description Chikungunya virus (CHIKV) is an arthropod-borne virus recently associated with large outbreaks in many parts of the world. Infection is typically manifested as a febrile and self-limited illness, characterized by joint pain and myalgia, albeit severe neurological manifestations are also reported. Although CHIKV is not recognized as a truly neurotropic virus, neurons, astrocytes, and oligodendrocytes are susceptible to infection in vitro. Here we employed a model of 3D cell culture to obtain neurospheres from ATRA/BNDF differentiated human neuroblastoma cells. We demonstrate that CHIKV is able to establish a productive infection, resulting in ultrastructural changes in cell morphology and impaired neuronal differentiation. Ultrastructural analysis of neurospheres infected with CHIKV during neuronal differentiation revealed diminished neuron dendrite formation, accumulation of viral particles associated with the plasma membrane, numerous cell vacuoles, and swollen mitochondria. Apoptotic cells were significantly increased at 72 h post-infection. Compared to Zika virus, a well-characterized neurotropic arbovirus, CHIKV infection resulted in a more discrete, albeit detectable upregulation of IL-6 levels. Finally, we found that CHIKV infection resulted in an altered profile expression, mainly downregulation, of a group of transcription factors named Hox genes. Altogether our findings highlight important features of CHIKV in the CNS, as well as the feasibility of neurospheres as robust experimental models that can support further studies for novel pharmacological interventions.
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spelling pubmed-102139242023-05-27 Chikungunya virus infection induces ultrastructural changes and impaired neuronal differentiation of human neurospheres de Lima Cavalcanti, Thaíse Yasmine Vasconcelos Azevedo, Elisa de Almeida Neves Lima, Morganna Costa Saraiva, Karina Lidiane Alcântara Franca, Rafael Freitas Oliveira Front Microbiol Microbiology Chikungunya virus (CHIKV) is an arthropod-borne virus recently associated with large outbreaks in many parts of the world. Infection is typically manifested as a febrile and self-limited illness, characterized by joint pain and myalgia, albeit severe neurological manifestations are also reported. Although CHIKV is not recognized as a truly neurotropic virus, neurons, astrocytes, and oligodendrocytes are susceptible to infection in vitro. Here we employed a model of 3D cell culture to obtain neurospheres from ATRA/BNDF differentiated human neuroblastoma cells. We demonstrate that CHIKV is able to establish a productive infection, resulting in ultrastructural changes in cell morphology and impaired neuronal differentiation. Ultrastructural analysis of neurospheres infected with CHIKV during neuronal differentiation revealed diminished neuron dendrite formation, accumulation of viral particles associated with the plasma membrane, numerous cell vacuoles, and swollen mitochondria. Apoptotic cells were significantly increased at 72 h post-infection. Compared to Zika virus, a well-characterized neurotropic arbovirus, CHIKV infection resulted in a more discrete, albeit detectable upregulation of IL-6 levels. Finally, we found that CHIKV infection resulted in an altered profile expression, mainly downregulation, of a group of transcription factors named Hox genes. Altogether our findings highlight important features of CHIKV in the CNS, as well as the feasibility of neurospheres as robust experimental models that can support further studies for novel pharmacological interventions. Frontiers Media S.A. 2023-05-11 /pmc/articles/PMC10213924/ /pubmed/37250062 http://dx.doi.org/10.3389/fmicb.2023.1152480 Text en Copyright © 2023 de Lima Cavalcanti, Azevedo, Lima, Saraiva and Franca. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
de Lima Cavalcanti, Thaíse Yasmine Vasconcelos
Azevedo, Elisa de Almeida Neves
Lima, Morganna Costa
Saraiva, Karina Lidiane Alcântara
Franca, Rafael Freitas Oliveira
Chikungunya virus infection induces ultrastructural changes and impaired neuronal differentiation of human neurospheres
title Chikungunya virus infection induces ultrastructural changes and impaired neuronal differentiation of human neurospheres
title_full Chikungunya virus infection induces ultrastructural changes and impaired neuronal differentiation of human neurospheres
title_fullStr Chikungunya virus infection induces ultrastructural changes and impaired neuronal differentiation of human neurospheres
title_full_unstemmed Chikungunya virus infection induces ultrastructural changes and impaired neuronal differentiation of human neurospheres
title_short Chikungunya virus infection induces ultrastructural changes and impaired neuronal differentiation of human neurospheres
title_sort chikungunya virus infection induces ultrastructural changes and impaired neuronal differentiation of human neurospheres
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10213924/
https://www.ncbi.nlm.nih.gov/pubmed/37250062
http://dx.doi.org/10.3389/fmicb.2023.1152480
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