Genomic and serologic characterization of enterovirus A71 brainstem encephalitis
Open Access
- 1 May 2020
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Neurology Neuroimmunology & Neuroinflammation
Abstract
Objective In 2016, Catalonia experienced a pediatric brainstem encephalitis outbreak caused by enterovirus A71 (EV-A71). Conventional testing identified EV in the periphery but rarely in CSF. Metagenomic next-generation sequencing (mNGS) and CSF pan-viral serology (VirScan) were deployed to enhance viral detection and characterization. Methods RNA was extracted from the CSF (n = 20), plasma (n = 9), stool (n = 15), and nasopharyngeal samples (n = 16) from 10 children with brainstem encephalitis and 10 children with meningitis or encephalitis. Pathogens were identified using mNGS. Available CSF from cases (n = 12) and pediatric other neurologic disease controls (n = 54) were analyzed with VirScan with a subset (n = 9 and n = 50) validated by ELISA. Results mNGS detected EV in all samples positive by quantitative reverse transcription polymerase chain reaction (qRT-PCR) (n = 25). In qRT-PCR-negative samples (n = 35), mNGS found virus in 23% (n = 8, 3 CSF samples). Overall, mNGS enhanced EV detection from 42% (25/60) to 57% (33/60) (p-value = 0.013). VirScan and ELISA increased detection to 92% (11/12) compared with 46% (4/12) for CSF mNGS and qRT-PCR (p-value = 0.023). Phylogenetic analysis confirmed the EV-A71 strain clustered with a neurovirulent German EV-A71. A single amino acid substitution (S241P) in the EVA71 VP1 protein was exclusive to the CNS in one subject. Conclusion mNGS with VirScan significantly increased the CNS detection of EVs relative to qRT-PCR, and the latter generated an antigenic profile of the acute EV-A71 immune response. Genomic analysis confirmed the close relation of the outbreak EV-A71 and neuroinvasive German EV-A71. A S241P substitution in VP1 was found exclusively in the CSF.Keywords
This publication has 40 references indexed in Scilit:
- Molecular epidemiology of enterovirus 71, coxsackievirus A16 and A6 associated with hand, foot and mouth disease in SpainClinical Microbiology & Infection, 2014
- Understanding the Direction of Bias in Studies of Diagnostic Test AccuracyAcademic Emergency Medicine, 2013
- Enterovirus 71 Binding to PSGL-1 on Leukocytes: VP1-145 Acts as a Molecular Switch to Control Receptor InteractionPLoS Pathogens, 2013
- SPAdes: A New Genome Assembly Algorithm and Its Applications to Single-Cell SequencingJournal of Computational Biology, 2012
- The Association of Recombination Events in the Founding and Emergence of Subgenogroup Evolutionary Lineages of Human Enterovirus 71Journal of Virology, 2012
- Comparison of an in-house real-time RT-PCR assay with a commercial assay for detection of enterovirus RNA in clinical samplesEuropean Journal of Clinical Microbiology & Infectious Diseases, 2011
- Human P-selectin glycoprotein ligand-1 is a functional receptor for enterovirus 71Nature Medicine, 2009
- Molecular epidemiological study of HEV‐B enteroviruses involved in the increase in meningitis cases occurred in Spain during 2006Journal of Medical Virology, 2008
- Outbreak of Neurologic Enterovirus Type 71 Disease: A Diagnostic ChallengeClinical Infectious Diseases, 2007
- Frequency and Dynamics of Recombination within Different Species of Human EnterovirusesJournal of Virology, 2006