1. 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
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Penpicha Chankeeree, Kantinan Leetanasaksakul, Boonlert Lumlertdacha, Wanapinun Nawae, Nanchaya Wanasen, Porntippa Lekcharoensuk, Sira Sriswasdi, Sithichoke Tangphatsornruang, Thanakorn Jaemthaworn, Thanathom Chailangkarn, Yuparat Jantraphakorn, Challika Kaewborisuth, and Nathiphat Tanwattana
- Subjects
Cell type ,Cytoskeleton organization ,Proteome ,Rabies ,QH301-705.5 ,Induced Pluripotent Stem Cells ,neurons ,virus–host interaction ,Biology ,medicine.disease_cause ,Article ,Catalysis ,Inorganic Chemistry ,medicine ,human-induced pluripotent stem cells ,Humans ,rabies virus ,Physical and Theoretical Chemistry ,Biology (General) ,Induced pluripotent stem cell ,Molecular Biology ,QD1-999 ,Spectroscopy ,Cells, Cultured ,Organic Chemistry ,Rabies virus ,proteomics analysis ,General Medicine ,medicine.disease ,Synaptic vesicle cycle ,Computer Science Applications ,Chemistry ,in vitro model ,Host-Pathogen Interactions ,Neuropathogenesis ,Neurotransmitter transport ,Neuroscience - 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.
- Published
- 2021