Whole-Exome Sequencing of Patients With Recurrent HSV-2 Lymphocytic Mollaret Meningitis
Autor: | Mette Christiansen, Maibritt Mardahl, Alon Schneider Hait, Christian Brandt, Simon Muller Larsen, Michelle M. Thomsen, Trine H. Mogensen, Toke S. Barfod, Marie Helleberg |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
autophagy recurrent HSV-2 meningitis Herpesvirus 2 Human Disease medicine.disease_cause Lymphocytic choriomeningitis 03 medical and health sciences 0302 clinical medicine Immune system Immunity Interferon Recurrence Exome Sequencing medicine Immunology and Allergy Humans Meningitis Lymphocytes whole-exome sequencing Exome sequencing business.industry Herpes Simplex interferon medicine.disease 3. Good health 030104 developmental biology Infectious Diseases Herpes simplex virus Immunology Interferons business 030217 neurology & neurosurgery medicine.drug |
Zdroj: | 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, vol. 223, no. 10, pp. 1776-1786 . https://doi.org/10.1093/infdis/jiaa589 |
Popis: | 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. |
Databáze: | OpenAIRE |
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