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

• Autor(a) principal: Soniza Vieira Alves Leon
• Data de Publicação: 2021
• Outros Autores: Luiza Mendonça Higa, Ana Paula de Campos Guimarães, Mariane Talon de Menezes, Marcelo Calado de Paula Tôrres, Richard Araújo Maia, Bruno Miceli Gonzalez Nogueira, Laise Carolina França, Marcos Martins da Silva, Christian Naurath, Cristina dos Santos Ferreira, Aline Saraiva da Silva Correia, Claudia Cristina Ferreira Vasconcelos, Orlando Costa Ferreira, Cynthia Chester Cardoso, Renato Santana de Aguiar, Ana Tereza Ribeiro de Vasconcelos, Alice Laschuk Herlinger, Fabrícia Lima Fontes Dantas, Fernanda Rueda Lopes, Ronaldo da Silva Francisco, João Paulo da Costa Gonçalves, Amanda Dutra de Araújo, Cláudia Cecília da Silva Rêgo, Alexandra Lehmkuhl Gerber, Amilcar Tanuri
• Tipo de documento: Artigo
• Idioma: por
• Título da fonte: Repositório Institucional da UFMG
• Texto Completo: https://doi.org/10.3389/fgene.2021.639364; http://hdl.handle.net/1843/56479; https://orcid.org/0000-0002-1538-6730; https://orcid.org/0000-0001-6587-3871; https://orcid.org/0000-0001-7931-3963; https://orcid.org/0000-0001-8851-7845; https://orcid.org/0000-0003-1770-607X; https://orcid.org/0000-0002-5870-5068; https://orcid.org/0000-0001-9096-5751; https://orcid.org/0000-0001-5180-3717; https://orcid.org/0000-0002-4632-2086; https://orcid.org/0000-0002-7660-7058; https://orcid.org/0000-0002-5201-0927; https://orcid.org/0000-0002-3782-8624; https://orcid.org/0000-0001-5724-6106; https://orcid.org/0000-0003-0570-750X
• topic: Whole exome sequence; Chikungunya; Pathogenic variants; HLA alleles; Inflammatory demyelinating diseases; Neurological manifestations in viral infection; Acute disseminated encephalomyelitis; Myelitis; Chikungunya; Bacterias patogenicas; Doenças inflamatórias; Encefalomielite

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 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.