Exome-Wide Search for Genes Associated With Central Nervous System Inflammatory Demyelinating Diseases Following CHIKV Infection: The Tip of the Iceberg.

Autor:	Alves-Leon SV; Translational Neuroscience Laboratory, Rio de Janeiro State Federal University, Rio de Janeiro, Brazil.; Department of Neurology/Reference and Research Center for Multiple Sclerosis and Other Central Nervous System Idiopathic Demyelinating Inflammatory Diseases, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Ferreira CDS; Bioinformatics Laboratory, National Laboratory for Scientific Computing, Petrópolis, Brazil., Herlinger AL; Molecular Virology Laboratory, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Fontes-Dantas FL; Translational Neuroscience Laboratory, Rio de Janeiro State Federal University, Rio de Janeiro, Brazil., Rueda-Lopes FC; Department of Radiology, Antônio Pedro University Hospital, Fluminense Federal University, Niterói, Brazil., Francisco RDS Jr; Bioinformatics Laboratory, National Laboratory for Scientific Computing, Petrópolis, Brazil., Gonçalves JPDC; Translational Neuroscience Laboratory, Rio de Janeiro State Federal University, Rio de Janeiro, Brazil.; Department of Neurology/Reference and Research Center for Multiple Sclerosis and Other Central Nervous System Idiopathic Demyelinating Inflammatory Diseases, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., de Araújo AD; Translational Neuroscience Laboratory, Rio de Janeiro State Federal University, Rio de Janeiro, Brazil.; Department of Neurology/Reference and Research Center for Multiple Sclerosis and Other Central Nervous System Idiopathic Demyelinating Inflammatory Diseases, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Rêgo CCDS; Translational Neuroscience Laboratory, Rio de Janeiro State Federal University, Rio de Janeiro, Brazil.; Department of Neurology/Reference and Research Center for Multiple Sclerosis and Other Central Nervous System Idiopathic Demyelinating Inflammatory Diseases, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Higa LM; Molecular Virology Laboratory, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Gerber AL; Bioinformatics Laboratory, National Laboratory for Scientific Computing, Petrópolis, Brazil., Guimarães APC; Bioinformatics Laboratory, National Laboratory for Scientific Computing, Petrópolis, Brazil., de Menezes MT; Molecular Virology Laboratory, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., de Paula Tôrres MC; Molecular Virology Laboratory, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Maia RA; Molecular Virology Laboratory, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Nogueira BMG; Translational Neuroscience Laboratory, Rio de Janeiro State Federal University, Rio de Janeiro, Brazil., França LC; Translational Neuroscience Laboratory, Rio de Janeiro State Federal University, Rio de Janeiro, Brazil., da Silva MM; Department of Clinical Medicine, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Naurath C; Federal Hospital Cardoso Fontes, Ministry of Health, Rio de Janeiro, Brazil., Correia ASDS; Federal Hospital Cardoso Fontes, Ministry of Health, Rio de Janeiro, Brazil., Vasconcelos CCF; Department of Neurology, University Hospital Gafrée e Guinle, Rio de Janeiro State Federal University, Rio de Janeiro, Brazil., Tanuri A; Molecular Virology Laboratory, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Ferreira OC Jr; Molecular Virology Laboratory, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Cardoso CC; Molecular Virology Laboratory, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Aguiar RS; Department of Genetics, Ecology and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil., de Vasconcelos ATR; Bioinformatics Laboratory, National Laboratory for Scientific Computing, Petrópolis, Brazil.
Jazyk:	angličtina
Zdroj:	Frontiers in genetics [Front Genet] 2021 Mar 17; Vol. 12, pp. 639364. Date of Electronic Publication: 2021 Mar 17 (Print Publication: 2021).
DOI:	10.3389/fgene.2021.639364
Abstrakt:	Chikungunya virus (CHIKV) is a re-emergent arbovirus that causes a disease characterized primarily by fever, rash and severe persistent polyarthralgia, although <1% of cases develop severe neurological manifestations such as inflammatory demyelinating diseases (IDD) of the central nervous system (CNS) like acute disseminated encephalomyelitis (ADEM) and extensive transverse myelitis. Genetic factors associated with host response and disease severity are still poorly understood. In this study, we performed whole-exome sequencing (WES) to identify HLA alleles, genes and cellular pathways associated with CNS IDD clinical phenotype outcomes following CHIKV infection. The cohort includes 345 patients of which 160 were confirmed for CHIKV. Six cases presented neurological manifestation mimetizing CNS IDD. WES data analysis was performed for 12 patients, including the CNS IDD cases and 6 CHIKV patients without any neurological manifestation. We identified 29 candidate genes harboring rare, pathogenic, or probably pathogenic variants in all exomes analyzed. HLA alleles were also determined and patients who developed CNS IDD shared a common signature with diseases such as Multiple sclerosis (MS) and Neuromyelitis Optica Spectrum Disorders (NMOSD). When these genes were included in Gene Ontology analyses, pathways associated with CNS IDD syndromes were retrieved, suggesting that CHIKV-induced CNS outcomesmay share a genetic background with other neurological disorders. To our knowledge, this study was the first genome-wide investigation of genetic risk factors for CNS phenotypes in CHIKV infection. Our data suggest that HLA-DRB1 alleles associated with demyelinating diseases may also confer risk of CNS IDD outcomes in patients with CHIKV infection. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Alves-Leon, Ferreira, Herlinger, Fontes-Dantas, Rueda-Lopes, Francisco, Gonçalves, de Araújo, Rêgo, Higa, Gerber, Guimarães, de Menezes, de Paula Tôrres, Maia, Nogueira, França, da Silva, Naurath, Correia, Vasconcelos, Tanuri, Ferreira, Cardoso, Aguiar and de Vasconcelos.)
Databáze:	MEDLINE
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