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Viral Metagenomics on Cerebrospinal Fluid
Open AccessArticle

Viral Sequences Detection by High-Throughput Sequencing in Cerebrospinal Fluid of Individuals with and without Central Nervous System Disease

1
Laboratory of Virology, Laboratory Medicine Division, Diagnostic Department, Geneva University Hospitals, 1205 Geneva, Switzerland
2
Swiss Institute of Bioinformatics, 1206 Geneva, Switzerland
3
Department of Genetic Medicine and Development, Faculty of Medicine of Geneva, 1206 Geneva, Switzerland
4
Paediatric Infectious Diseases Unit, Department of Women-Children-Teenagers, Geneva University Hospitals and Medical School, 1205 Geneva, Switzerland
5
Infectious Diseases Service, Hospital Clinic-IDIBAPS, University of Barcelona, 08036 Barcelona, Spain
6
iGE3 Genomics Platform, University of Geneva, 1206 Geneva, Switzerland
7
Anaesthesiology Division, Department of Anaesthesiology, Pharmacology, Intensive Care and Emergency Medicine, Geneva University Hospitals, 1205 Geneva, Switzerland
8
Faculty of Medicine of Geneva, University of Geneva, 1205 Geneva, Switzerland
*
Author to whom correspondence should be addressed.
Equal contribution.
Genes 2019, 10(8), 625; https://doi.org/10.3390/genes10080625
Received: 11 July 2019 / Revised: 12 August 2019 / Accepted: 14 August 2019 / Published: 19 August 2019
(This article belongs to the Special Issue Viral Diagnostics Using Next-Generation Sequencing)
Meningitis, encephalitis, and myelitis are various forms of acute central nervous system (CNS) inflammation, which can coexist and lead to serious sequelae. Known aetiologies include infections and immune-mediated processes. Despite advances in clinical microbiology over the past decades, the cause of acute CNS inflammation remains unknown in approximately 50% of cases. High-throughput sequencing was performed to search for viral sequences in cerebrospinal fluid (CSF) samples collected from 26 patients considered to have acute CNS inflammation of unknown origin, and 10 patients with defined causes of CNS diseases. In order to better grasp the clinical significance of viral sequence data obtained in CSF, 30 patients without CNS disease who had a lumbar puncture performed during elective spinal anaesthesia were also analysed. One case of human astrovirus (HAstV)-MLB2-related meningitis and disseminated infection was identified. No other viral sequences that can easily be linked to CNS inflammation were detected. Viral sequences obtained in all patient groups are discussed. While some of them reflect harmless viral infections, others result from reagent or sample contamination, as well as index hopping. Altogether, this study highlights the potential of high-throughput sequencing in identifying previously unknown viral neuropathogens, as well as the interpretation issues related to its application in clinical microbiology. View Full-Text
Keywords: acute central nervous system inflammation; meningitis; encephalitis; myelitis; high throughput sequencing; viruses; cerebrospinal fluid; viral sequences acute central nervous system inflammation; meningitis; encephalitis; myelitis; high throughput sequencing; viruses; cerebrospinal fluid; viral sequences
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Schibler, M.; Brito, F.; Zanella, M.-C.; Zdobnov, E.M.; Laubscher, F.; L’Huillier, A.G.; Ambrosioni, J.; Wagner, N.; Posfay-Barbe, K.M.; Docquier, M.; Schiffer, E.; Savoldelli, G.L.; Fournier, R.; Lenggenhager, L.; Cordey, S.; Kaiser, L. Viral Sequences Detection by High-Throughput Sequencing in Cerebrospinal Fluid of Individuals with and without Central Nervous System Disease. Genes 2019, 10, 625.

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