Viral infection and brain inflammation with seizures in PARK7 deficiency

Respiratory syncytial virus (RSV) is a major health problem worldwide, particularly in infants and young children. 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's 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's 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. Collectively, our results demonstrate a role for PARK7 in regulation of inflammation and cellular homeostasis and suggest that PARK7 deficiency may aggravate infectious disease and cause immunopathology.