MHC Variants Associated With Symptomatic Versus Asymptomatic SARS-CoV-2 Infection in Highly Exposed Individuals
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.3389/fimmu.2021.742881 http://hdl.handle.net/11449/231531 |
Resumo: | 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. |
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MHC Variants Associated With Symptomatic Versus Asymptomatic SARS-CoV-2 Infection in Highly Exposed IndividualsasymptomaticCOVID-19HLAMHCMICAMICBresistanceSARS-CoV-2Despite 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.Center for Information TechnologyCenter for Scientific ReviewNational Institutes of HealthOffice of Extramural Research, National Institutes of HealthOffice of Research Infrastructure Programs, National Institutes of HealthCoordenação 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)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 PauloDepartment of Genetics and Evolutionary Biology Biosciences Institute University of São PauloCentro Universitário Sudoeste PaulistaDepartamento de Química Faculdade de Filosofa Ciências e Letras de Ribeirão Preto Universidade de São PauloDepartment of Clinical and Toxicological Analyses School of Pharmaceutical Sciences University of São PauloDepartamento de Clínica Médica Disciplina de Alergia e Imunologia Clínica Faculdade de Medicina da Universidade de São PauloLaboratório 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-INCTDepartment 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: 001FAPESP: 2013/08028-1FAPESP: 2013/17084-0FAPESP: 2014/50931-3FAPESP: 2017/19223-0FAPESP: 2019/19998-8FAPESP: 2020/09702-1CNPq: 465355/2014-5Universidade Estadual Paulista (UNESP)Universidade de São Paulo (USP)Centro Universitário Sudoeste PaulistaInstituto de Investigação em Imunologia - Instituto Nacional de Ciências e Tecnologia-iii-INCTCastelli, 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, DiogoNunes, KellyMatos, Larissa R. B.Silva, Monize V. R.Wang, Jaqueline Y. T.Esposito, JoyceCoria, Vivian R.Bortolin, Raul H.Hirata, Mario H.Magawa, Jhosiene Y.Cunha-Neto, EdecioCoelho, VerônicaSantos, Keity S.Marin, Maria Lucia C.Kalil, JorgeMitne-Neto, MiguelMaciel, Rui M. B.Passos-Bueno, Maria RitaZatz, Mayana2022-04-29T08:46:00Z2022-04-29T08:46:00Z2021-09-28info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.3389/fimmu.2021.742881Frontiers in Immunology, v. 12.1664-3224http://hdl.handle.net/11449/23153110.3389/fimmu.2021.7428812-s2.0-85117108854Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengFrontiers in Immunologyinfo:eu-repo/semantics/openAccess2024-06-24T14:51:52Zoai:repositorio.unesp.br:11449/231531Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T20:14:07.989304Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
MHC Variants Associated With Symptomatic Versus Asymptomatic SARS-CoV-2 Infection in Highly Exposed Individuals |
title |
MHC Variants Associated With Symptomatic Versus Asymptomatic SARS-CoV-2 Infection in Highly Exposed Individuals |
spellingShingle |
MHC Variants Associated With Symptomatic Versus Asymptomatic SARS-CoV-2 Infection in Highly Exposed Individuals Castelli, Erick C. [UNESP] asymptomatic COVID-19 HLA MHC MICA MICB resistance SARS-CoV-2 |
title_short |
MHC Variants Associated With Symptomatic Versus Asymptomatic SARS-CoV-2 Infection in Highly Exposed Individuals |
title_full |
MHC Variants Associated With Symptomatic Versus Asymptomatic SARS-CoV-2 Infection in Highly Exposed Individuals |
title_fullStr |
MHC Variants Associated With Symptomatic Versus Asymptomatic SARS-CoV-2 Infection in Highly Exposed Individuals |
title_full_unstemmed |
MHC Variants Associated With Symptomatic Versus Asymptomatic SARS-CoV-2 Infection in Highly Exposed Individuals |
title_sort |
MHC Variants Associated With Symptomatic Versus Asymptomatic SARS-CoV-2 Infection in Highly Exposed Individuals |
author |
Castelli, Erick C. [UNESP] |
author_facet |
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 |
author_role |
author |
author2 |
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 |
author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (UNESP) Universidade de São Paulo (USP) Centro Universitário Sudoeste Paulista Instituto de Investigação em Imunologia - Instituto Nacional de Ciências e Tecnologia-iii-INCT |
dc.contributor.author.fl_str_mv |
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 |
dc.subject.por.fl_str_mv |
asymptomatic COVID-19 HLA MHC MICA MICB resistance SARS-CoV-2 |
topic |
asymptomatic COVID-19 HLA MHC MICA MICB resistance SARS-CoV-2 |
description |
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. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-09-28 2022-04-29T08:46:00Z 2022-04-29T08:46:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.3389/fimmu.2021.742881 Frontiers in Immunology, v. 12. 1664-3224 http://hdl.handle.net/11449/231531 10.3389/fimmu.2021.742881 2-s2.0-85117108854 |
url |
http://dx.doi.org/10.3389/fimmu.2021.742881 http://hdl.handle.net/11449/231531 |
identifier_str_mv |
Frontiers in Immunology, v. 12. 1664-3224 10.3389/fimmu.2021.742881 2-s2.0-85117108854 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Frontiers in Immunology |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1808129176953159680 |