MHC Variants Associated With Symptomatic Versus Asymptomatic SARS-CoV-2 Infection in Highly Exposed Individuals

Detalhes bibliográficos
Autor(a) principal: Castelli, Erick C. [UNESP]
Data de Publicação: 2021
Outros Autores: 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
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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spelling 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
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