Parechovirus-3 infection disrupts immunometabolism and leads to glutamate excitotoxicity in neural organoids
Year: 2025
Type: article
Abstract: Parechovirus ahumpari 3 (HPeV-3) is among the main agents causing severe neonatal neurological infections such as encephalitis and meningitis. However, the underlying molecular mechanisms and changes to the host cellular landscape leading to neurological disease has been understudied. Through quantitative proteomic analysis of HPeV-3 infected neural organoids, we identified unique metabolic changes following HPeV-3 infection that indicate immunometabolic dysregulation. Protein and pathway analyses showed significant alterations in neurotransmission and potentially, neuronal excitotoxicity. Elevated levels of extracellular glutamate, lactate dehydrogenase (LDH), and neurofilament light (NfL) confirmed glutamate excitotoxicity to be a key mechanism contributing to neuronal toxicity in HPeV-3 infection and can lead to apoptosis induced by caspase signaling. These insights are pivotal in delineating the metabolic landscape following severe HPeV-3 CNS infection and may identify potential host targets for therapeutic interventions.
Language: English
Topic: Virology and Viral Diseases
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,290
Awards: Comprehensive mapping of metabolic perturbations in emerging and re-emerging RNA viruses for novel therapeutic approaches, GUT VIrus BRain Axis Technology In OrgaNoid Science, Organoids for Virus Research - An innovative training-ETN programme, G434337789, Potentiating host immuno-metabolism as a novel approach toward reservoir eradication and functional cure in HIV-1 infection, G6344844147
OpenAlex ID: W4415926116