Genetic variants and immune responses in a cohort of patients with varicella zoster virus encephalitis

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  • Michelle M Thomsen
  • ,
  • Tobias Tyrberg, University of Gothenburg
  • ,
  • Kristoffer Skaalum
  • Madalina Carter-Timofte
  • Mette R Freytag
  • ,
  • Peter Norberg, University of Gothenburg
  • ,
  • Marie Helleberg, University of Copenhagen
  • ,
  • Merete Storgaard
  • Henrik Nielsen, Aalborg University
  • ,
  • Jacob Bodilsen, Aalborg University
  • ,
  • Anna Grahn, Sahlgrenska University Hospital, Gothenburg, Sweden; Institute of Health and Caring Sciences, The Sahlgrenska Academy, University of Gothenburg, Sweden.
  • ,
  • Trine Mogensen

BACKGROUND: Infection with varicella zoster virus (VZV) may involve different central nervous system (CNS) manifestations, including meningitis, encephalitis, and vasculitis. In cases where otherwise healthy individuals are affected, an inborn error of immunity may underlie increased susceptibility or severity of infection.

METHODS: We collected a cohort of 17 adults who experienced VZV encephalitis and performed whole exome sequencing. Patient PBMCs were infected with VZV and innate antiviral interferon and cytokine responses as well as viral replication was evaluated. Data were analyzed by Mann Whitney U test.

RESULTS: We identified a total of 21 different potentially disease-causing variants in a total of 13 of the 17 patients included. These gene variants were within two major functional clusters: i) innate viral sensors and immune pathways and ii) autophagy pathways. Antiviral interferon (IFN) and cytokine responses were abnormal in the majority of patients, whereas viral replication was increased in only 2/17.

CONCLUSION: This study identifies a list of variants of pathogenic potential, which may serve as a platform for generating hypotheses for future studies addressing genetic and immunological factors associated with susceptibility to VZV encephalitis. Collectively, these data suggest that disturbances in innate sensing and autophagy pathways may predispose to VZV encephalitis.

Original languageEnglish
JournalThe Journal of Infectious Diseases
Pages (from-to)2122-2132
Number of pages11
Publication statusPublished - Dec 2021

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