Molecular Mimicry between SARS-CoV-2 Proteins and Human Self-Antigens Related with Autoimmune Central Nervous System (CNS) Disorders
SARS-CoV-2 can trigger autoimmune central nervous system (CNS) diseases in genetically susceptible individuals, a mechanism poorly understood. Molecular mimicry (MM) has been identified in other viral diseases as potential triggers of autoimmune CNS events. This study investigated if MM is the proce...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-12-01
|
| Series: | Microorganisms |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-2607/11/12/2902 |
| _version_ | 1797379987246940160 |
|---|---|
| author | Elisa Gouvea Gutman Renan Amphilophio Fernandes Jéssica Vasques Raposo-Vedovi Andreza Lemos Salvio Larissa Araujo Duarte Caio Faria Tardim Vinicius Gabriel Coutinho Costa Valéria Coelho Santa Rita Pereira Paulo Roberto Valle Bahia Marcos Martins da Silva Fabrícia Lima Fontes-Dantas Soniza Vieira Alves-Leon |
| author_facet | Elisa Gouvea Gutman Renan Amphilophio Fernandes Jéssica Vasques Raposo-Vedovi Andreza Lemos Salvio Larissa Araujo Duarte Caio Faria Tardim Vinicius Gabriel Coutinho Costa Valéria Coelho Santa Rita Pereira Paulo Roberto Valle Bahia Marcos Martins da Silva Fabrícia Lima Fontes-Dantas Soniza Vieira Alves-Leon |
| author_sort | Elisa Gouvea Gutman |
| collection | DOAJ |
| description | SARS-CoV-2 can trigger autoimmune central nervous system (CNS) diseases in genetically susceptible individuals, a mechanism poorly understood. Molecular mimicry (MM) has been identified in other viral diseases as potential triggers of autoimmune CNS events. This study investigated if MM is the process through which SARS-CoV-2 induces the breakdown of immune tolerance. The frequency of autoimmune CNS disorders was evaluated in a prospective cohort with patients admitted to the COVID-19 Intense Care Unity (ICU) in Rio de Janeiro. Then, an in silico analysis was performed to identify the conserved regions that share a high identity between SARS-CoV-2 antigens and human proteins. The sequences with significant identity and antigenic properties were then assessed for their binding capacity to HLA subtypes. Of the 112 patients included, 3 were classified as having an autoimmune disorder. A total of eleven combinations had significant linear and three-dimensional overlap. NMDAR1, MOG, and MPO were the self-antigens with more significant combinations, followed by GAD65. All sequences presented at least one epitope with strong or intermediate binding capacity to the HLA subtypes selected. This study underscores the possibility that CNS autoimmune attacks observed in COVID-19 patients, including those in our population, could be driven by MM in genetically predisposed individuals. |
| first_indexed | 2024-03-08T20:30:58Z |
| format | Article |
| id | doaj.art-74ea3f8e2d4a4acf928ac8f0a23c11ac |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-08T20:30:58Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-74ea3f8e2d4a4acf928ac8f0a23c11ac2023-12-22T14:26:00ZengMDPI AGMicroorganisms2076-26072023-12-011112290210.3390/microorganisms11122902Molecular Mimicry between SARS-CoV-2 Proteins and Human Self-Antigens Related with Autoimmune Central Nervous System (CNS) DisordersElisa Gouvea Gutman0Renan Amphilophio Fernandes1Jéssica Vasques Raposo-Vedovi2Andreza Lemos Salvio3Larissa Araujo Duarte4Caio Faria Tardim5Vinicius Gabriel Coutinho Costa6Valéria Coelho Santa Rita Pereira7Paulo Roberto Valle Bahia8Marcos Martins da Silva9Fabrícia Lima Fontes-Dantas10Soniza Vieira Alves-Leon11Translational Neuroscience Laboratory (LabNet), Biomedical Institute, Federal University of the State of Rio de Janeiro, Rio de Janeiro 20211-030, RJ, BrazilTranslational Neuroscience Laboratory (LabNet), Biomedical Institute, Federal University of the State of Rio de Janeiro, Rio de Janeiro 20211-030, RJ, BrazilTranslational Neuroscience Laboratory (LabNet), Biomedical Institute, Federal University of the State of Rio de Janeiro, Rio de Janeiro 20211-030, RJ, BrazilTranslational Neuroscience Laboratory (LabNet), Biomedical Institute, Federal University of the State of Rio de Janeiro, Rio de Janeiro 20211-030, RJ, BrazilTranslational Neuroscience Laboratory (LabNet), Biomedical Institute, Federal University of the State of Rio de Janeiro, Rio de Janeiro 20211-030, RJ, BrazilDepartment of Neurology, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, RJ, BrazilMorphological Sciences Post-Graduation Program, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, RJ, BrazilDepartment of Neurology, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, RJ, BrazilDepartment of Radiology, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, RJ, BrazilDepartment of Neurology, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, RJ, BrazilDepartment of Pharmacology, Institute of Biology, Rio de Janeiro State University, Rio de Janeiro 20950-000, RJ, BrazilTranslational Neuroscience Laboratory (LabNet), Biomedical Institute, Federal University of the State of Rio de Janeiro, Rio de Janeiro 20211-030, RJ, BrazilSARS-CoV-2 can trigger autoimmune central nervous system (CNS) diseases in genetically susceptible individuals, a mechanism poorly understood. Molecular mimicry (MM) has been identified in other viral diseases as potential triggers of autoimmune CNS events. This study investigated if MM is the process through which SARS-CoV-2 induces the breakdown of immune tolerance. The frequency of autoimmune CNS disorders was evaluated in a prospective cohort with patients admitted to the COVID-19 Intense Care Unity (ICU) in Rio de Janeiro. Then, an in silico analysis was performed to identify the conserved regions that share a high identity between SARS-CoV-2 antigens and human proteins. The sequences with significant identity and antigenic properties were then assessed for their binding capacity to HLA subtypes. Of the 112 patients included, 3 were classified as having an autoimmune disorder. A total of eleven combinations had significant linear and three-dimensional overlap. NMDAR1, MOG, and MPO were the self-antigens with more significant combinations, followed by GAD65. All sequences presented at least one epitope with strong or intermediate binding capacity to the HLA subtypes selected. This study underscores the possibility that CNS autoimmune attacks observed in COVID-19 patients, including those in our population, could be driven by MM in genetically predisposed individuals.https://www.mdpi.com/2076-2607/11/12/2902COVID-19SARS-CoV-2molecular mimicryimmune toleranceautoimmune disorderscentral nervous system |
| spellingShingle | Elisa Gouvea Gutman Renan Amphilophio Fernandes Jéssica Vasques Raposo-Vedovi Andreza Lemos Salvio Larissa Araujo Duarte Caio Faria Tardim Vinicius Gabriel Coutinho Costa Valéria Coelho Santa Rita Pereira Paulo Roberto Valle Bahia Marcos Martins da Silva Fabrícia Lima Fontes-Dantas Soniza Vieira Alves-Leon Molecular Mimicry between SARS-CoV-2 Proteins and Human Self-Antigens Related with Autoimmune Central Nervous System (CNS) Disorders Microorganisms COVID-19 SARS-CoV-2 molecular mimicry immune tolerance autoimmune disorders central nervous system |
| title | Molecular Mimicry between SARS-CoV-2 Proteins and Human Self-Antigens Related with Autoimmune Central Nervous System (CNS) Disorders |
| title_full | Molecular Mimicry between SARS-CoV-2 Proteins and Human Self-Antigens Related with Autoimmune Central Nervous System (CNS) Disorders |
| title_fullStr | Molecular Mimicry between SARS-CoV-2 Proteins and Human Self-Antigens Related with Autoimmune Central Nervous System (CNS) Disorders |
| title_full_unstemmed | Molecular Mimicry between SARS-CoV-2 Proteins and Human Self-Antigens Related with Autoimmune Central Nervous System (CNS) Disorders |
| title_short | Molecular Mimicry between SARS-CoV-2 Proteins and Human Self-Antigens Related with Autoimmune Central Nervous System (CNS) Disorders |
| title_sort | molecular mimicry between sars cov 2 proteins and human self antigens related with autoimmune central nervous system cns disorders |
| topic | COVID-19 SARS-CoV-2 molecular mimicry immune tolerance autoimmune disorders central nervous system |
| url | https://www.mdpi.com/2076-2607/11/12/2902 |
| work_keys_str_mv | AT elisagouveagutman molecularmimicrybetweensarscov2proteinsandhumanselfantigensrelatedwithautoimmunecentralnervoussystemcnsdisorders AT renanamphilophiofernandes molecularmimicrybetweensarscov2proteinsandhumanselfantigensrelatedwithautoimmunecentralnervoussystemcnsdisorders AT jessicavasquesraposovedovi molecularmimicrybetweensarscov2proteinsandhumanselfantigensrelatedwithautoimmunecentralnervoussystemcnsdisorders AT andrezalemossalvio molecularmimicrybetweensarscov2proteinsandhumanselfantigensrelatedwithautoimmunecentralnervoussystemcnsdisorders AT larissaaraujoduarte molecularmimicrybetweensarscov2proteinsandhumanselfantigensrelatedwithautoimmunecentralnervoussystemcnsdisorders AT caiofariatardim molecularmimicrybetweensarscov2proteinsandhumanselfantigensrelatedwithautoimmunecentralnervoussystemcnsdisorders AT viniciusgabrielcoutinhocosta molecularmimicrybetweensarscov2proteinsandhumanselfantigensrelatedwithautoimmunecentralnervoussystemcnsdisorders AT valeriacoelhosantaritapereira molecularmimicrybetweensarscov2proteinsandhumanselfantigensrelatedwithautoimmunecentralnervoussystemcnsdisorders AT paulorobertovallebahia molecularmimicrybetweensarscov2proteinsandhumanselfantigensrelatedwithautoimmunecentralnervoussystemcnsdisorders AT marcosmartinsdasilva molecularmimicrybetweensarscov2proteinsandhumanselfantigensrelatedwithautoimmunecentralnervoussystemcnsdisorders AT fabricialimafontesdantas molecularmimicrybetweensarscov2proteinsandhumanselfantigensrelatedwithautoimmunecentralnervoussystemcnsdisorders AT sonizavieiraalvesleon molecularmimicrybetweensarscov2proteinsandhumanselfantigensrelatedwithautoimmunecentralnervoussystemcnsdisorders |