{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T22:44:42Z","timestamp":1788561882860,"version":"build-2803163510"},"reference-count":97,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T00:00:00Z","timestamp":1636070400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Thailand Science Research and Innovation (TSRI)","award":["6280011"],"award-info":[{"award-number":["6280011"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2013host 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.<\/jats:p>","DOI":"10.3390\/ijms222111986","type":"journal-article","created":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T10:33:09Z","timestamp":1636108389000},"page":"11986","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Establishment of Human-Induced Pluripotent Stem Cell-Derived Neurons\u2014A Promising In Vitro Model for a Molecular Study of Rabies Virus and Host Interaction"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3556-1775","authenticated-orcid":false,"given":"Thanathom","family":"Chailangkarn","sequence":"first","affiliation":[{"name":"Virology and Cell Technology Research Team, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathum Thani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathiphat","family":"Tanwattana","sequence":"additional","affiliation":[{"name":"Interdisciplinary Program in Genetic Engineering and Bioinformatics, Graduate School, Kasetsart University, Bangkok 10900, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanakorn","family":"Jaemthaworn","sequence":"additional","affiliation":[{"name":"Computational Molecular Biology Group, Chulalongkorn University, Pathum Wan, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4117-3632","authenticated-orcid":false,"given":"Sira","family":"Sriswasdi","sequence":"additional","affiliation":[{"name":"Computational Molecular Biology Group, Chulalongkorn University, Pathum Wan, Bangkok 10330, Thailand"},{"name":"Research Affairs, Faculty of Medicine, Chulalongkorn University, Pathum Wan, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanchaya","family":"Wanasen","sequence":"additional","affiliation":[{"name":"Virology and Cell Technology Research Team, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathum Thani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2673-0012","authenticated-orcid":false,"given":"Sithichoke","family":"Tangphatsornruang","sequence":"additional","affiliation":[{"name":"National Omics Center, National Science and Technology Development Agency (NSTDA), Pathum Thani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3396-4562","authenticated-orcid":false,"given":"Kantinan","family":"Leetanasaksakul","sequence":"additional","affiliation":[{"name":"Functional Proteomics Technology, Functional Ingredients and Food Innovation Research Group, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathum Thani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5503-2136","authenticated-orcid":false,"given":"Yuparat","family":"Jantraphakorn","sequence":"additional","affiliation":[{"name":"Virology and Cell Technology Research Team, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathum Thani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9228-6963","authenticated-orcid":false,"given":"Wanapinun","family":"Nawae","sequence":"additional","affiliation":[{"name":"National Omics Center, National Science and Technology Development Agency (NSTDA), Pathum Thani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Penpicha","family":"Chankeeree","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Veterinary Medicine, Kasetsart University, Bangkok 10900, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5595-3296","authenticated-orcid":false,"given":"Porntippa","family":"Lekcharoensuk","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Veterinary Medicine, Kasetsart University, Bangkok 10900, Thailand"},{"name":"Center for Advance Studies in Agriculture and Food, KU Institute Studies, Kasetsart University, Bangkok 10900, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boonlert","family":"Lumlertdacha","sequence":"additional","affiliation":[{"name":"Queen Saovabha Memorial Institute, Thai Red Cross Society, WHO Collaborating Center for Research and Training Prophylaxis on Rabies, 1871 Rama 4 Road, Pathumwan, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3477-3784","authenticated-orcid":false,"given":"Challika","family":"Kaewborisuth","sequence":"additional","affiliation":[{"name":"Virology and Cell Technology Research Team, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathum Thani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1080\/13550280590900427","article-title":"Rabies Virus Receptors","volume":"11","author":"Lafon","year":"2005","journal-title":"J. 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