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Immunol."],"abstract":"<jats:p>Human parechovirus type 3 (PeV-A3) infection has been recognized as an emerging etiologic factor causing severe nerve disease or sepsis in infants and young children. But the neuropathogenic mechanisms of PeV-A3 remain unknown. To understand the pathogenesis of PeV-A3 infection in the neuronal system, PeV-A3-mediated cytopathic effects were analyzed in human glioblastoma cells and neuroblastoma cells. PeV-A3 induced interferons and inflammatory cytokine expression in these neuronal cells. The pronounced cytopathic effects accompanied with activation of death signaling pathways of apoptosis, autophagy, and pyroptosis were detected. A new experimental disease model of parechovirus encephalitis was established. In the disease model, intracranial inoculation with PeV-A3 in C57BL\/6 neonatal mice showed body weight loss, hindlimb paralysis, and approximately 20% mortality. PeV-A3 infection in the hippocampus and cortex regions of the neonatal mouse brain was revealed. Mechanistic assay supported the <jats:italic>in vitro<\/jats:italic> results, indicating detection of PeV-A3 replication, inflammatory cytokine expression, and death signaling transduction in mouse brain tissues. These <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> studies revealed that the activation of death signaling and inflammation responses is involved in PeV-A3-mediated neurological disorders. The present results might account for some of the PeV-A3-associated clinical manifestations.<\/jats:p>","DOI":"10.3389\/fimmu.2021.753683","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T23:31:13Z","timestamp":1638315073000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Characterization of Pathogenesis and Inflammatory Responses to Experimental Parechovirus 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