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

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

*Corresponding author af dette arbejde

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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.

OriginalsprogEngelsk
TidsskriftThe Journal of Infectious Diseases
Vol/bind223
Nummer10
Sider (fra-til)1776-1786
Antal sider11
ISSN0022-1899
DOI
StatusUdgivet - maj 2021

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