The immunodominant antibody response to Zika virus NS1 protein is characterized by cross-reactivity to self
| Autor: | Leda R. Castilho, Luciana Conde, Alberto Nobrega, Jonas N. Conde, Bruno Maia, Andre M. Vale, Ronaldo Mohana-Borges, Cecilia B. Cavazzoni, Renata G. F. Alvim, Heitor A. Paula Neto, Tostes C V Lucas, Gabriel D. Victora, Iranaia Assunção-Miranda, Rômulo L. S. Neris, Tulio M. Lima, Vicente B. T. Bozza, Diego R. Coelho, Luka Mesin, Jonatan Ersching, Ariën Schiepers |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
viruses Immunology Immunodominance Cross Reactions Viral Nonstructural Proteins medicine.disease_cause Antibodies Viral Cross-reactivity Immunoglobulin G Virus Zika virus 03 medical and health sciences 0302 clinical medicine Antigen medicine Immunology and Allergy Animals Antigens Viral B-Lymphocytes Mice Inbred BALB C biology Zika Virus Infection virus diseases Germinal center biochemical phenomena metabolism and nutrition biology.organism_classification Germinal Center Virology 030104 developmental biology Immunoglobulin M biology.protein Female Immunization Antibody 030215 immunology |
| Zdroj: | The Journal of experimental medicine. 218(9) |
| ISSN: | 1540-9538 |
| Popis: | Besides antigen-specific responses to viral antigens, humoral immune response in virus infection can generate polyreactive and autoreactive antibodies. Dengue and Zika virus infections have been linked to antibody-mediated autoimmune disorders, including Guillain-Barré syndrome. A unique feature of flaviviruses is the secretion of nonstructural protein 1 (NS1) by infected cells. NS1 is highly immunogenic, and antibodies targeting NS1 can have both protective and pathogenic roles. In the present study, we investigated the humoral immune response to Zika virus NS1 and found NS1 to be an immunodominant viral antigen associated with the presence of autoreactive antibodies. Through single B cell cultures, we coupled binding assays and BCR sequencing, confirming the immunodominance of NS1. We demonstrate the presence of self-reactive clones in germinal centers after both infection and immunization, some of which present cross-reactivity with NS1. Sequence analysis of anti-NS1 B cell clones showed sequence features associated with pathogenic autoreactive antibodies. Our findings demonstrate NS1 immunodominance at the cellular level as well as a potential role for NS1 in ZIKV-associated autoimmune manifestations. |
| Databáze: | OpenAIRE |
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