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

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dc.creatorSoniza Vieira Alves Leon
dc.creatorLuiza Mendonça Higa
dc.creatorAna Paula de Campos Guimarães
dc.creatorMariane Talon de Menezes
dc.creatorMarcelo Calado de Paula Tôrres
dc.creatorRichard Araújo Maia
dc.creatorBruno Miceli Gonzalez Nogueira
dc.creatorLaise Carolina França
dc.creatorMarcos Martins da Silva
dc.creatorChristian Naurath
dc.creatorCristina dos Santos Ferreira
dc.creatorAline Saraiva da Silva Correia
dc.creatorClaudia Cristina Ferreira Vasconcelos
dc.creatorOrlando Costa Ferreira
dc.creatorCynthia Chester Cardoso
dc.creatorRenato Santana de Aguiar
dc.creatorAna Tereza Ribeiro de Vasconcelos
dc.creatorAlice Laschuk Herlinger
dc.creatorFabrícia Lima Fontes Dantas
dc.creatorFernanda Rueda Lopes
dc.creatorRonaldo da Silva Francisco
dc.creatorJoão Paulo da Costa Gonçalves
dc.creatorAmanda Dutra de Araújo
dc.creatorCláudia Cecília da Silva Rêgo
dc.creatorAlexandra Lehmkuhl Gerber
dc.creatorAmilcar Tanuri
dc.date.accessioned2023-07-17T19:59:36Z
dc.date.accessioned2025-09-09T00:50:43Z
dc.date.available2023-07-17T19:59:36Z
dc.date.issued2021
dc.identifier.doihttps://doi.org/10.3389/fgene.2021.639364
dc.identifier.issn1664-8021
dc.identifier.urihttps://hdl.handle.net/1843/56479
dc.languagepor
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofFrontiers in Genetics
dc.rightsAcesso Aberto
dc.subjectChikungunya
dc.subjectBacterias patogenicas
dc.subjectDoenças inflamatórias
dc.subjectEncefalomielite
dc.subject.otherWhole exome sequence
dc.subject.otherChikungunya
dc.subject.otherPathogenic variants
dc.subject.otherHLA alleles
dc.subject.otherInflammatory demyelinating diseases
dc.subject.otherNeurological manifestations in viral infection
dc.subject.otherAcute disseminated encephalomyelitis
dc.subject.otherMyelitis
dc.titleExome-Wide Search for Genes Associated With Central Nervous System Inflammatory Demyelinating Diseases Following CHIKV Infection: the Tip of the Iceberg
dc.typeArtigo de periódico
local.citation.epage13
local.citation.spage1
local.citation.volume12
local.description.resumoChikungunya 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 demyelinatingdiseases(IDD)ofthecentralnervoussystem(CNS)likeacutedisseminated 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 CNSoutcomesmayshareageneticbackgroundwithotherneurologicaldisorders.Toour knowledge, this study was the first genome-wide investigation of genetic risk factors for CNS phenotypes in CHIKV infection. Our data suggest thatHLA-DRB1 allelesassociated with demyelinating diseases may also confer risk of CNS IDD outcomes in patients with CHIKV infection.
local.identifier.orcidhttps://orcid.org/0000-0002-1538-6730
local.identifier.orcidhttps://orcid.org/0000-0001-6587-3871
local.identifier.orcidhttps://orcid.org/0000-0001-7931-3963
local.identifier.orcidhttps://orcid.org/0000-0001-8851-7845
local.identifier.orcidhttps://orcid.org/0000-0003-1770-607X
local.identifier.orcidhttps://orcid.org/0000-0002-5870-5068
local.identifier.orcidhttps://orcid.org/0000-0001-9096-5751
local.identifier.orcidhttps://orcid.org/0000-0001-5180-3717
local.identifier.orcidhttps://orcid.org/0000-0002-4632-2086
local.identifier.orcidhttps://orcid.org/0000-0002-7660-7058
local.identifier.orcidhttps://orcid.org/0000-0002-5201-0927
local.identifier.orcidhttps://orcid.org/0000-0002-3782-8624
local.identifier.orcidhttps://orcid.org/0000-0001-5724-6106
local.identifier.orcidhttps://orcid.org/0000-0003-0570-750X
local.publisher.countryBrasil
local.publisher.departmentICB - INSTITUTO DE CIÊNCIAS BIOLOGICAS
local.publisher.initialsUFMG
local.url.externahttps://www.frontiersin.org/articles/10.3389/fgene.2021.639364/full

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