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

Michelle M Thomsen, Tobias Tyrberg, Kristoffer Skaalum, Madalina Carter-Timofte, Mette R Freytag, Peter Norberg, Marie Helleberg, Merete Storgaard, Henrik Nielsen, Jacob Bodilsen, Anna Grahn, Trine Mogensen*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

7 Citations (Scopus)

Abstract

BACKGROUND: Infection with varicella zoster virus (VZV) may involve different central nervous system (CNS) manifestations, including meningitis, encephalitis, and vasculitis. In cases in which 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 peripheral blood mononuclear cells were infected with VZV, and innate antiviral interferon (IFN) and cytokine responses as well as viral replication were 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 2 major functional clusters: (1) innate viral sensors and immune pathways and (2) autophagy pathways. Antiviral IFN and cytokine responses were abnormal in the majority of patients, whereas viral replication was increased in only 2 of 17 patients.

CONCLUSIONS: 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. These data, taken together, suggest that disturbances in innate sensing and autophagy pathways may predispose to VZV encephalitis.

Original languageEnglish
JournalThe Journal of Infectious Diseases
Volume224
Issue number12
Pages (from-to)2122–2132
Number of pages11
ISSN0022-1899
DOIs
Publication statusPublished - 15 Dec 2021

Bibliographical note

© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Keywords

  • autophagy
  • inborn error of immunity
  • interferon
  • varicella zoster virus
  • whole exome sequencing

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