-
Establishment of human-induced pluripotent stem cell-derived neurons—a promising in vitro model for a molecular study of rabies virus and host interaction
- Back
Metadata
Document 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
Author
Chailangkarn T.,Tanwattana N.,Jaemthaworn T.,Sriswasdi S.,Wanasen N.,Tangphatsornruang S.,Leetanasaksakul K.,Jantraphakorn Y.,Nawae W.,Chankeeree P.,Lekcharoensuk P.,Lumlertdacha B.,Kaewborisuth C.
Name from Authors Collection
Affiliations
Virology and Cell Technology Research Team, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani12120, Thailand; Interdisciplinary Program in Genetic Engineering and Bioinformatics, Graduate School, Kasetsart University, Bangkok, 10900, Thailand; Computational Molecular Biology Group, Chulalongkorn University, Pathum Wan, Bangkok, 10330, Thailand; Research Affairs, Faculty of Medicine, Chulalongkorn University, Pathum Wan, Bangkok, 10330, Thailand; National Omics Center, National Science and Technology Development Agency (NSTDA), Pathumthani12120, Thailand; 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), Pathumthani12120, Thailand; Department of Microbiology and Immunology, Faculty of Veterinary Medicine, Kasetsart University, Bangkok, 10900, Thailand; Center for Advance Studies in Agriculture and Food, KU Institute Studies, Kasetsart University, Bangkok, 10900, Thailand; 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
Type
Article
Source Title
International Journal of Molecular Sciences
ISSN
16616596
Year
2021
Volume
22
Issue
21
Open Access
All Open Access, Gold, Green
Publisher
MDPI
DOI
10.3390/ijms222111986
Abstract
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. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Industrial Classification
Knowledge Taxonomy Level 1
Knowledge Taxonomy Level 2
Knowledge Taxonomy Level 3
License
CC BY
Rights
Author
Publication Source
Scopus