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

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

Authors :
Alves-Leon SV
Ferreira CDS
Herlinger AL
Fontes-Dantas FL
Rueda-Lopes FC
Francisco RDS Jr
Gonçalves JPDC
de Araújo AD
Rêgo CCDS
Higa LM
Gerber AL
Guimarães APC
de Menezes MT
de Paula Tôrres MC
Maia RA
Nogueira BMG
França LC
da Silva MM
Naurath C
Correia ASDS
Vasconcelos CCF
Tanuri A
Ferreira OC Jr
Cardoso CC
Aguiar RS
de Vasconcelos ATR
Source :
Frontiers in genetics [Front Genet] 2021 Mar 17; Vol. 12, pp. 639364. Date of Electronic Publication: 2021 Mar 17 (Print Publication: 2021).
Publication Year :
2021

Abstract

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.<br />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.<br /> (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.)

Details

Language :
English
ISSN :
1664-8021
Volume :
12
Database :
MEDLINE
Journal :
Frontiers in genetics
Publication Type :
Academic Journal
Accession number :
33815474
Full Text :
https://doi.org/10.3389/fgene.2021.639364