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Establishment of Human-Induced Pluripotent Stem Cell-Derived Neurons—A Promising In Vitro Model for a Molecular Study of Rabies Virus and Host Interaction

Rabies is a deadly viral disease caused by the rabies virus (RABV), transmitted through a bite of an infected host, resulting in irreversible neurological symptoms and a 100% fatality rate in humans. Despite many aspects describing rabies neuropathogenesis, numerous hypotheses remain unanswered and...

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Autores principales: Chailangkarn, Thanathom, Tanwattana, Nathiphat, Jaemthaworn, Thanakorn, Sriswasdi, Sira, Wanasen, Nanchaya, Tangphatsornruang, Sithichoke, Leetanasaksakul, Kantinan, Jantraphakorn, Yuparat, Nawae, Wanapinun, Chankeeree, Penpicha, Lekcharoensuk, Porntippa, Lumlertdacha, Boonlert, Kaewborisuth, Challika
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584829/
https://www.ncbi.nlm.nih.gov/pubmed/34769416
http://dx.doi.org/10.3390/ijms222111986
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author Chailangkarn, Thanathom
Tanwattana, Nathiphat
Jaemthaworn, Thanakorn
Sriswasdi, Sira
Wanasen, Nanchaya
Tangphatsornruang, Sithichoke
Leetanasaksakul, Kantinan
Jantraphakorn, Yuparat
Nawae, Wanapinun
Chankeeree, Penpicha
Lekcharoensuk, Porntippa
Lumlertdacha, Boonlert
Kaewborisuth, Challika
author_facet Chailangkarn, Thanathom
Tanwattana, Nathiphat
Jaemthaworn, Thanakorn
Sriswasdi, Sira
Wanasen, Nanchaya
Tangphatsornruang, Sithichoke
Leetanasaksakul, Kantinan
Jantraphakorn, Yuparat
Nawae, Wanapinun
Chankeeree, Penpicha
Lekcharoensuk, Porntippa
Lumlertdacha, Boonlert
Kaewborisuth, Challika
author_sort Chailangkarn, Thanathom
collection PubMed
description Rabies is a deadly viral disease caused by the rabies virus (RABV), transmitted through a bite of an infected host, resulting in irreversible neurological symptoms and a 100% fatality rate in humans. Despite many aspects describing rabies neuropathogenesis, numerous hypotheses remain unanswered and concealed. Observations obtained from infected primary neurons or mouse brain samples are more relevant to human clinical rabies than permissive cell lines; however, limitations regarding the ethical issue and sample accessibility become a hurdle for discovering new insights into virus–host interplays. To better understand RABV pathogenesis in humans, we generated human-induced pluripotent stem cell (hiPSC)-derived neurons to offer the opportunity for an inimitable study of RABV infection at a molecular level in a pathologically relevant cell type. This study describes the characteristics and detailed proteomic changes of hiPSC-derived neurons in response to RABV infection using LC-MS/MS quantitative analysis. Gene ontology (GO) enrichment of differentially expressed proteins (DEPs) reveals temporal changes of proteins related to metabolic process, immune response, neurotransmitter transport/synaptic vesicle cycle, cytoskeleton organization, and cell stress response, demonstrating fundamental underlying mechanisms of neuropathogenesis in a time-course dependence. Lastly, we highlighted plausible functions of heat shock cognate protein 70 (HSC70 or HSPA8) that might play a pivotal role in regulating RABV replication and pathogenesis. Our findings acquired from this hiPSC-derived neuron platform help to define novel cellular mechanisms during RABV infection, which could be applicable to further studies to widen views of RABV-host interaction.
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spelling pubmed-85848292021-11-12 Establishment of Human-Induced Pluripotent Stem Cell-Derived Neurons—A Promising In Vitro Model for a Molecular Study of Rabies Virus and Host Interaction Chailangkarn, Thanathom Tanwattana, Nathiphat Jaemthaworn, Thanakorn Sriswasdi, Sira Wanasen, Nanchaya Tangphatsornruang, Sithichoke Leetanasaksakul, Kantinan Jantraphakorn, Yuparat Nawae, Wanapinun Chankeeree, Penpicha Lekcharoensuk, Porntippa Lumlertdacha, Boonlert Kaewborisuth, Challika Int J Mol Sci Article Rabies is a deadly viral disease caused by the rabies virus (RABV), transmitted through a bite of an infected host, resulting in irreversible neurological symptoms and a 100% fatality rate in humans. Despite many aspects describing rabies neuropathogenesis, numerous hypotheses remain unanswered and concealed. Observations obtained from infected primary neurons or mouse brain samples are more relevant to human clinical rabies than permissive cell lines; however, limitations regarding the ethical issue and sample accessibility become a hurdle for discovering new insights into virus–host interplays. To better understand RABV pathogenesis in humans, we generated human-induced pluripotent stem cell (hiPSC)-derived neurons to offer the opportunity for an inimitable study of RABV infection at a molecular level in a pathologically relevant cell type. This study describes the characteristics and detailed proteomic changes of hiPSC-derived neurons in response to RABV infection using LC-MS/MS quantitative analysis. Gene ontology (GO) enrichment of differentially expressed proteins (DEPs) reveals temporal changes of proteins related to metabolic process, immune response, neurotransmitter transport/synaptic vesicle cycle, cytoskeleton organization, and cell stress response, demonstrating fundamental underlying mechanisms of neuropathogenesis in a time-course dependence. Lastly, we highlighted plausible functions of heat shock cognate protein 70 (HSC70 or HSPA8) that might play a pivotal role in regulating RABV replication and pathogenesis. Our findings acquired from this hiPSC-derived neuron platform help to define novel cellular mechanisms during RABV infection, which could be applicable to further studies to widen views of RABV-host interaction. MDPI 2021-11-05 /pmc/articles/PMC8584829/ /pubmed/34769416 http://dx.doi.org/10.3390/ijms222111986 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chailangkarn, Thanathom
Tanwattana, Nathiphat
Jaemthaworn, Thanakorn
Sriswasdi, Sira
Wanasen, Nanchaya
Tangphatsornruang, Sithichoke
Leetanasaksakul, Kantinan
Jantraphakorn, Yuparat
Nawae, Wanapinun
Chankeeree, Penpicha
Lekcharoensuk, Porntippa
Lumlertdacha, Boonlert
Kaewborisuth, Challika
Establishment of Human-Induced Pluripotent Stem Cell-Derived Neurons—A Promising In Vitro Model for a Molecular Study of Rabies Virus and Host Interaction
title Establishment of Human-Induced Pluripotent Stem Cell-Derived Neurons—A Promising In Vitro Model for a Molecular Study of Rabies Virus and Host Interaction
title_full Establishment of Human-Induced Pluripotent Stem Cell-Derived Neurons—A Promising In Vitro Model for a Molecular Study of Rabies Virus and Host Interaction
title_fullStr Establishment of Human-Induced Pluripotent Stem Cell-Derived Neurons—A Promising In Vitro Model for a Molecular Study of Rabies Virus and Host Interaction
title_full_unstemmed Establishment of Human-Induced Pluripotent Stem Cell-Derived Neurons—A Promising In Vitro Model for a Molecular Study of Rabies Virus and Host Interaction
title_short Establishment of Human-Induced Pluripotent Stem Cell-Derived Neurons—A Promising In Vitro Model for a Molecular Study of Rabies Virus and Host Interaction
title_sort establishment of human-induced pluripotent stem cell-derived neurons—a promising in vitro model for a molecular study of rabies virus and host interaction
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584829/
https://www.ncbi.nlm.nih.gov/pubmed/34769416
http://dx.doi.org/10.3390/ijms222111986
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