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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MDPI AG
2021
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oai:doaj.org-article:a377047a319d4dc7916091f169266e512021-11-11T17:24:23ZEstablishment of Human-Induced Pluripotent Stem Cell-Derived Neurons—A Promising In Vitro Model for a Molecular Study of Rabies Virus and Host Interaction10.3390/ijms2221119861422-00671661-6596https://doaj.org/article/a377047a319d4dc7916091f169266e512021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11986https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Rabies 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.Thanathom ChailangkarnNathiphat TanwattanaThanakorn JaemthawornSira SriswasdiNanchaya WanasenSithichoke TangphatsornruangKantinan LeetanasaksakulYuparat JantraphakornWanapinun NawaePenpicha ChankeereePorntippa LekcharoensukBoonlert LumlertdachaChallika KaewborisuthMDPI AGarticlehuman-induced pluripotent stem cellsin vitro modelneuronsrabies virusproteomics analysisvirus–host interactionBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11986, p 11986 (2021) |
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human-induced pluripotent stem cells in vitro model neurons rabies virus proteomics analysis virus–host interaction Biology (General) QH301-705.5 Chemistry QD1-999 |
| spellingShingle |
human-induced pluripotent stem cells in vitro model neurons rabies virus proteomics analysis virus–host interaction Biology (General) QH301-705.5 Chemistry QD1-999 Thanathom Chailangkarn Nathiphat Tanwattana Thanakorn Jaemthaworn Sira Sriswasdi Nanchaya Wanasen Sithichoke Tangphatsornruang Kantinan Leetanasaksakul Yuparat Jantraphakorn Wanapinun Nawae Penpicha Chankeeree Porntippa Lekcharoensuk Boonlert Lumlertdacha Challika Kaewborisuth Establishment of Human-Induced Pluripotent Stem Cell-Derived Neurons—A Promising In Vitro Model for a Molecular Study of Rabies Virus and Host Interaction |
| 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. |
| format |
article |
| author |
Thanathom Chailangkarn Nathiphat Tanwattana Thanakorn Jaemthaworn Sira Sriswasdi Nanchaya Wanasen Sithichoke Tangphatsornruang Kantinan Leetanasaksakul Yuparat Jantraphakorn Wanapinun Nawae Penpicha Chankeeree Porntippa Lekcharoensuk Boonlert Lumlertdacha Challika Kaewborisuth |
| author_facet |
Thanathom Chailangkarn Nathiphat Tanwattana Thanakorn Jaemthaworn Sira Sriswasdi Nanchaya Wanasen Sithichoke Tangphatsornruang Kantinan Leetanasaksakul Yuparat Jantraphakorn Wanapinun Nawae Penpicha Chankeeree Porntippa Lekcharoensuk Boonlert Lumlertdacha Challika Kaewborisuth |
| author_sort |
Thanathom Chailangkarn |
| 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_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_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_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 |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/a377047a319d4dc7916091f169266e51 |
| work_keys_str_mv |
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