# Viral infection and brain inflammation with seizures in PARK7 deficiency

## TL;DR

A child with a PARK7 gene deficiency experienced severe RSV infection, brain inflammation, and seizures, highlighting PARK7's role in immune regulation and disease susceptibility.

## Contribution

First association of PARK7 deficiency with RSV-induced brain inflammation and seizures, revealing PARK7's role in immune and cellular homeostasis.

## Key findings

- PARK7 deficiency leads to increased inflammatory cytokine responses and impaired RSV-induced apoptosis.
- PARK7-deficient neuronal cells showed similar cellular phenotypes as the patient, reversed by PARK7 reconstitution.
- PARK7 deficiency may aggravate infectious diseases and cause immunopathology.

## Abstract

Here, Lønskov et al. describe a child homozygous for a deleterious variant in PARK7/DJ-1 presenting with RSV infection, brain inflammation, and seizures and explore the pathophysiology of PARK7 deficiency, underscoring the importance of PARK7 in human immune regulation and homeostasis.

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.