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Hait AS, Thomsen MM, Larsen SM, et al. Whole-Exome Sequencing of Patients With Recurrent HSV-2 Lymphocytic Mollaret Meningitis. J Infect Dis. 2021;223(10):1776-1786doi: 10.1093/infdis/jiaa589.
Hait, A. S., Thomsen, M. M., Larsen, S. M., Helleberg, M., Mardahl, M., Barfod, T. S., Christiansen, M., Brandt, C., & Mogensen, T. H. (2021). Whole-Exome Sequencing of Patients With Recurrent HSV-2 Lymphocytic Mollaret Meningitis. The Journal of infectious diseases, 223(10), 1776-1786. https://doi.org/10.1093/infdis/jiaa589
Hait, Alon Schneider, et al. "Whole-Exome Sequencing of Patients With Recurrent HSV-2 Lymphocytic Mollaret Meningitis." The Journal of infectious diseases vol. 223,10 (2021): 1776-1786. doi: https://doi.org/10.1093/infdis/jiaa589
Hait AS, Thomsen MM, Larsen SM, Helleberg M, Mardahl M, Barfod TS, Christiansen M, Brandt C, Mogensen TH. Whole-Exome Sequencing of Patients With Recurrent HSV-2 Lymphocytic Mollaret Meningitis. J Infect Dis. 2021 May 28;223(10):1776-1786. doi: 10.1093/infdis/jiaa589. PMID: 32946550.
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J Infect Dis. 2021 May 28;223(10):1776-1786. doi: 10.1093/infdis/jiaa589.

Whole-Exome Sequencing of Patients With Recurrent HSV-2 Lymphocytic Mollaret Meningitis.

The Journal of infectious diseases

Alon Schneider Hait, Michelle M Thomsen, Simon M Larsen, Marie Helleberg, Maibritt Mardahl, Toke S Barfod, Mette Christiansen, Christian Brandt, Trine H Mogensen

Affiliations

  1. Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
  2. Department of Biomedicine, Aarhus University, Aarhus, Denmark.
  3. Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
  4. Department of Internal medicine, Section for Infectious Diseases, Zealand University Hospital, Roskilde, Denmark.
  5. Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
  6. Department of Pulmonology and Infectious Diseases, Nordsjællands Hospital, Hillerød, Denmark.
  7. Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.

PMID: 32946550 DOI: 10.1093/infdis/jiaa589

Abstract

Recurrent lymphocytic meningitis, also referred to as Mollaret meningitis, is a rare neurological disease characterized mainly by reactivation of herpes simplex virus 2 (HSV-2) from sensory ganglia. However, the underlying host immune determinants and viral factors rendering some individuals unable to maintain HSV-2 latency are largely unknown. We collected a cohort of 15 patients diagnosed with Mollaret meningitis. By whole-exome sequencing we identified rare host genetic variants predicted to be deleterious in molecules involved in (1) ubiquitin-proteasome pathways, (2) the autophagy machinery, and (3) cell proliferation/apoptosis. Moreover, infection of patient cells with HSV-2 or stimulation by virus-derived double-stranded DNA ligands revealed reduced antiviral interferon responses in most patients. These findings may contribute to a better understanding of disease pathogenesis and protective immunity to HSV in the central nervous system, and may ultimately be of importance for identification of targets for development of improved prophylaxis and treatment of this disease.

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].

Keywords: autophagy; interferon; recurrent HSV-2 meningitis; whole-exome sequencing

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