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

Author(s):Show less -

Castelli, Erick C. ^{[1, 2]} ; de Castro, V, Mateus ; Naslavsky, Michel S. ^{[3, 4]} ; Scliar, Marilia O. ^[4] ; Silva, Nayane S. B. ^[2] ; Andrade, Heloisa S. ^[2] ; Souza, Andreia S. ^[2] ; Pereira, Raphaela N. ^[2] ; Castro, Camila F. B. ^{[2, 5]} ; Mendes-Junior, Celso T. ^[6] ; Meyer, Diogo ^[3] ; Nunes, Kelly ^[3] ; Matos, Larissa R. B. ^[4] ; Silva, Monize V. R. ^[4] ; Wang, Jaqueline Y. T. ^[4] ; Esposito, Joyce ^[4] ; Coria, Vivian R. ^[4] ; Bortolin, Raul H. ^[7] ; Hirata, Mario H. ^[7] ; Magawa, Jhosiene Y. ^[8] ; Cunha-Neto, Edecio ^{[8, 9, 10]} ; Coelho, Veronica ^{[9, 10]} ; Santos, Keity S. ^{[8, 9, 10]} ; Marin, Maria Lucia C. ^{[9, 10]} ; Kalil, Jorge ^{[8, 9, 10]} ; Mitne-Neto, Miguel ^[11] ; Maciel, Rui M. B. ^[11] ; Passos-Bueno, Maria Rita ^{[3, 4]} ; Zatz, Mayana ^{[3, 4]}

Affiliation:Show less -

^[1] Sao Paulo State Univ UNESP, Sch Med, Dept Pathol, Botucatu, SP - Brazil

^[2] Sao Paulo State Univ UNESP, Sch Med, Mol Genet & Bioinformat Lab, Expt Res Unit, Botucatu, SP - Brazil

^[3] Univ Sao Paulo, Biosci Inst, Dept Genet & Evolutionary Biol, Sao Paulo - Brazil

^[4] de Castro, Mateus, V, Univ Sao Paulo, Human Genome & Stem Cell Res Ctr, Sao Paulo - Brazil

^[5] Ctr Univ Sudoeste Paulista, Avare - Brazil

^[6] Univ Sao Paulo, Fac Filosofa Ciencias & Letras Ribeirao Preto, Dept Quim, Ribeirao Preto - Brazil

^[7] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, Sao Paulo - Brazil

^[8] Univ Sao Paulo, Dept Clin Med, Disciplina Alergia & Imunol Clin, Fac Med, Sao Paulo - Brazil

^[9] Univ Sao Paulo, Inst Coracao InCor, Lab Imunol, HCFMUSP, Hosp Clin, Fac Med, LIM19, Sao Paulo - Brazil

^[10] Inst Nacl Ciencias & Tecnol III, Inst Invest Imunol, INCT, Sao Paulo - Brazil

^[11] Grp Fleury, Res & Dev, Sao Paulo - Brazil

• Document type: Journal article
• Source: FRONTIERS IN IMMUNOLOGY; v. 12, SEP 28 2021.
• Web of Science Citations: 0

Abstract

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.</p> (AU)

• FAPESP's process: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center
• Grantee: Mayana Zatz
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 19/19998-8 - Development of pipeline for copy number variation (CNVs) analysis
• Grantee: Marília de Oliveira Scliar
• Support Opportunities: Scholarships in Brazil - Technical Training Program - Technical Training
• FAPESP's process: 20/09702-1 - Study of protective genetic variants in resilient nonagenarians and centenarians
• Grantee: Mateus Vidigal de Castro
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/19223-0 - KIR2DL4, KIR3DL2, KIR3DL3, LILRB1 (ILT2) and LILRB2 (ILT4) variability and haplotypes in a Brazilian population sample from the São Paulo state
• Grantee: Erick da Cruz Castelli
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/50931-3 - Aging and genetic disorders: genomics and metagenomics
• Grantee: Mayana Zatz
• Support Opportunities: Research Projects - Thematic Grants