[en] Varicella-zoster virus (VZV) is a neurotropic member of the Herpesviridae family which causes varicella in primary infection and zoster during reactivation but in rare cases can lead to severe neurological complications, such as encephalitis. To identify inborn errors of immunity (IEI) and unravel pathways involved in VZV CNS immune responses and pathogenesis, we performed whole exome sequencing on a cohort of 38 children with neurological manifestations, including VZV encephalitis, cerebellitis, or stroke. We identified a total of 46 rare potentially pathogenic variants predicted to be deleterious, including variants in innate antiviral immunity, inflammation, cell stress responses, and autophagy. Collectively these findings represent a knowledge base for further functional studies and provide new insights into the genetic landscape of VZV CNS infections and highlight potential genetic defects that may compromise host defense, enabling new avenues for diagnosis and personalized treatment strategies for VZV CNS infections.
Disciplines :
Pediatrics Neurology
Author, co-author :
Winzig, Franziska ; Department of Biomedicine, Aarhus University, Aarhus, Denmark ; Center for Immunology for Viral Infections (CiViA), Aarhus University, Aarhus, Denmark
De Keukeleere, Kerstin; Department of Biomedicine, Aarhus University, Aarhus, Denmark ; Center for Immunology for Viral Infections (CiViA), Aarhus University, Aarhus, Denmark
Bartholomeus, Esther ; Antwerp Center for Translational Immunology and Virology (ACTIV), Vaccine and Infectious Disease Institute, University of Antwerp, Wilrijk, Belgium ; Center for Health Economics Research and Modelling Infectious Diseases (CHERMID), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Wilrijk, Belgium ; Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing (AUDACIS), University of Antwerp, Antwerp, Belgium
Deconinck, Nicolas; Department of Paediatric Neurology, Hôpital Universitaire de Bruxelles (HUB ; Hôpital Universitaire des Enfants Reine Fabiola (HUDERF ; Université Libre de Bruxelles, ULB, Brussels, Belgium
Barrea, Christophe ; Université de Liège - ULiège > Département des sciences cliniques > Médecine générale
Matthijs, Inge; Department of Paediatrics, AZ Delta, Roeselare, Belgium
Jansen, Anna C ; Division of Pediatric Neurology, Department of Pediatrics, Antwerp University Hospital, Edegem, Belgium ; Translational Neurosciences, University of Antwerp, Wilrijk, Belgium
Verhelst, Helene ; Department of Pediatrics, Division of Pediatric Neurology, Ghent University Hospital, Ghent, Belgium ; Faculty of Medicine and Health Sciences, Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
Dielman, Charlotte; Department of Paediatrics, Ziekenhuis Aan de Stroom (ZAS), Antwerp, Belgium
Kuznetsova, Maria ; Antwerp Center for Translational Immunology and Virology (ACTIV), Vaccine and Infectious Disease Institute, University of Antwerp, Wilrijk, Belgium ; Center for Health Economics Research and Modelling Infectious Diseases (CHERMID), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Wilrijk, Belgium ; Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing (AUDACIS), University of Antwerp, Antwerp, Belgium
Ha, My ; Antwerp Center for Translational Immunology and Virology (ACTIV), Vaccine and Infectious Disease Institute, University of Antwerp, Wilrijk, Belgium ; Center for Health Economics Research and Modelling Infectious Diseases (CHERMID), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Wilrijk, Belgium ; Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing (AUDACIS), University of Antwerp, Antwerp, Belgium
Suls, Arvid; Center of Medical Genetics, University of Antwerp
van der Sluis, Renee M ; Department of Biomedicine, Aarhus University, Aarhus, Denmark ; Center for Immunology for Viral Infections (CiViA), Aarhus University, Aarhus, Denmark
Ogunjimi, Benson; Antwerp Center for Translational Immunology and Virology (ACTIV), Vaccine and Infectious Disease Institute, University of Antwerp, Wilrijk, Belgium ; Center for Health Economics Research and Modelling Infectious Diseases (CHERMID), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Wilrijk, Belgium ; Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing (AUDACIS), University of Antwerp, Antwerp, Belgium ; Department of Paediatrics, Ziekenhuis Aan de Stroom (ZAS), Antwerp, Belgium ; Department of Paediatrics, Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium ; Department of Pediatrics, Antwerp University Hospital, Edegem, Belgium
Mogensen, Trine H ; Department of Biomedicine, Aarhus University, Aarhus, Denmark ; Center for Immunology for Viral Infections (CiViA), Aarhus University, Aarhus, Denmark ; Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark
