Viral infection and brain inflammation with seizures in PARK7 deficiency

Jonas Lønskov; Annika Sünderhauf; Sisse Andersen; Caroline Bækmann Jeppesen; Franziska Winzig; Daniëla Maria Hinke; Johanna L Heinz; Kenneth Thomsen; Mette B Thorup; Thomas Zillinger; Bettina Bundgaard; Kerstin De Keukeleere; Sofie Eg Jørgensen; Jakob Ek; Elsebet Østergaard; Jakob Christensen; Mette Møller Handrup; Renee M van der Sluis; Trine H Mogensen

doi:10.70962/jhi.20250044

Viral infection and brain inflammation with seizures in PARK7 deficiency

J Hum Immun. 2025 Dec 26;2(2):e20250044. doi: 10.70962/jhi.20250044. eCollection 2026 Mar 2.

Authors

Jonas Lønskov^#^{1

2}, Annika Sünderhauf^#^{1

2}, Sisse Andersen^#^{1

2}, Caroline Bækmann Jeppesen^{3

4}, Franziska Winzig^{1

2}, Daniëla Maria Hinke^{1

2}, Johanna L Heinz^{1

2}, Kenneth Thomsen⁵, Mette B Thorup⁶, Thomas Zillinger^{1

2

7}, Bettina Bundgaard^{1

2}, Kerstin De Keukeleere^{1

2}, Sofie Eg Jørgensen^{1

2}, Jakob Ek⁸, Elsebet Østergaard^{8

9}, Jakob Christensen^{3

10}, Mette Møller Handrup^{3

4}, Renee M van der Sluis^#^{1

2}, Trine H Mogensen^#^{1

2

11}

Affiliations

¹ Department of Biomedicine, Aarhus University, Aarhus, Denmark.
² Center for Immunology of Viral Infections, Aarhus University, Aarhus, Denmark.
³ Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
⁴ Department of Pediatrics, Rare Diseases, Aarhus University Hospital, Aarhus, Denmark.
⁵ Department of Dermatology and Venereology, Aarhus University Hospital, Aarhus, Denmark.
⁶ Department of Radiology, Aarhus University Hospital, Aarhus, Denmark.
⁷ Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany.
⁸ Department of Clinical Genetics, Rigshospitalet, Copenhagen, Denmark.
⁹ Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
¹⁰ Department of Neurology, Aarhus University Hospital, Aarhus, Denmark.
¹¹ Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.

^# Contributed equally.

Abstract

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.