Autor(es):
Castelli, Erick C. [UNESP] ; de Castro, Mateus V. ; Naslavsky, Michel S. ; Scliar, Marilia O. ; Silva, Nayane S. B. [UNESP] ; Andrade, Heloisa S. [UNESP] ; Souza, Andreia S. [UNESP] ; Pereira, Raphaela N. [UNESP] ; Castro, Camila F. B. [UNESP] ; Mendes-Junior, Celso T. ; Meyer, Diogo ; Nunes, Kelly ; Matos, Larissa R. B. ; Silva, Monize V. R. ; Wang, Jaqueline Y. T. ; Esposito, Joyce ; Coria, Vivian R. ; Bortolin, Raul H. ; Hirata, Mario H. ; Magawa, Jhosiene Y. ; Cunha-Neto, Edecio ; Coelho, Verônica ; Santos, Keity S. ; Marin, Maria Lucia C. ; Kalil, Jorge ; Mitne-Neto, Miguel ; Maciel, Rui M. B. ; Passos-Bueno, Maria Rita ; Zatz, Mayana
Data: 2022
Identificador Persistente: http://hdl.handle.net/11449/231531
Origem: Oasisbr
Assunto(s): asymptomatic; COVID-19; HLA; MHC; MICA; MICB; resistance; SARS-CoV-2
Descrição
Made available in DSpace on 2022-04-29T08:46:00Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-09-28
Center for Information Technology
Center for Scientific Review
National Institutes of Health
Office of Extramural Research, National Institutes of Health
Office of Research Infrastructure Programs, National Institutes of Health
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Despite the high number of individuals infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who develop coronavirus disease 2019 (COVID-19) symptoms worldwide, many exposed individuals remain asymptomatic and/or uninfected and seronegative. This could be explained by a combination of environmental (exposure), immunological (previous infection), epigenetic, and genetic factors. Aiming to identify genetic factors involved in immune response in symptomatic COVID-19 as compared to asymptomatic exposed individuals, we analyzed 83 Brazilian couples where one individual was infected and symptomatic while the partner remained asymptomatic and serum-negative for at least 6 months despite sharing the same bedroom during the infection. We refer to these as “discordant couples”. We performed whole-exome sequencing followed by a state-of-the-art method to call genotypes and haplotypes across the highly polymorphic major histocompatibility complex (MHC) region. The discordant partners had comparable ages and genetic ancestry, but women were overrepresented (65%) in the asymptomatic group. In the antigen-presentation pathway, we observed an association between HLA-DRB1 alleles encoding Lys at residue 71 (mostly DRB1*03:01 and DRB1*04:01) and DOB*01:02 with symptomatic infections and HLA-A alleles encoding 144Q/151R with asymptomatic seronegative women. Among the genes related to immune modulation, we detected variants in MICA and MICB associated with symptomatic infections. These variants are related to higher expression of soluble MICA and low expression of MICB. Thus, quantitative differences in these molecules that modulate natural killer (NK) activity could contribute to susceptibility to COVID-19 by downregulating NK cell cytotoxic activity in infected individuals but not in the asymptomatic partners.
Department of Pathology School of Medicine São Paulo State University (UNESP)
Molecular Genetics and Bioinformatics Laboratory–Experimental Research Unit School of Medicine São Paulo State University (UNESP)
Human Genome and Stem Cell Research Center University of São Paulo
Department of Genetics and Evolutionary Biology Biosciences Institute University of São Paulo
Centro Universitário Sudoeste Paulista
Departamento de Química Faculdade de Filosofa Ciências e Letras de Ribeirão Preto Universidade de São Paulo
Department of Clinical and Toxicological Analyses School of Pharmaceutical Sciences University of São Paulo
Departamento de Clínica Médica Disciplina de Alergia e Imunologia Clínica Faculdade de Medicina da Universidade de São Paulo
Laboratório de Imunologia Instituto do Coração (InCor) LIM19 Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP)
Instituto de Investigação em Imunologia - Instituto Nacional de Ciências e Tecnologia-iii-INCT
Department of Pathology School of Medicine São Paulo State University (UNESP)
Molecular Genetics and Bioinformatics Laboratory–Experimental Research Unit School of Medicine São Paulo State University (UNESP)
CAPES: 001
FAPESP: 2013/08028-1
FAPESP: 2013/17084-0
FAPESP: 2014/50931-3
FAPESP: 2017/19223-0
FAPESP: 2019/19998-8
FAPESP: 2020/09702-1
CNPq: 465355/2014-5
