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The infection can progress to life-threatening lower respiratory disease and, in rare cases, involves the central nervous system. We explore the pathophysiology in a child with high fever, seizures, and encephalopathy with brain inflammation during severe RSV infection. Whole-genome sequencing revealed homozygosity for a rare loss-of-function variant in the early-onset Parkinson-related gene PARK7\/DJ-1. PARK7 plays a role in immune regulation, stress responses, and cell death. The patient\u2019s Peripheral blood mononuclear cells and fibroblasts exhibited increased inflammatory cytokine responses, impaired RSV-induced apoptosis, and dampened autophagy. Studies in PARK7-deficient neuronal cells recapitulated the patient\u2019s cellular phenotype, which was reversed upon PARK7 reconstitution. To our knowledge, this is the first association between PARK7 deficiency and RSV-induced brain inflammation, encephalopathy, and seizures. 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