Structures of Two Human Astrovirus Capsid/Neutralizing Antibody Complexes Reveal Distinct Epitopes and Inhibition of Virus Attachment to Cells
| Autor: | Carolina Cuellar, Tomás López, Carlos F. Arias, Nayeli Aguilar-Hernández, Rafaela Espinosa, Sarah Lanning, Lena Ricemeyer, Rebecca M. DuBois, Susana López, Santanu Mukherjee |
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| Přispěvatelé: | Schultz-Cherry, Stacey |
| Rok vydání: | 2022 |
| Předmět: |
Models
Molecular viruses Antibody Affinity Molecular Conformation Antibodies Viral Medical and Health Sciences Epitope Epitopes astrovirus fluids and secretions Models Astroviridae Infections 2.1 Biological and endogenous factors Viral Neutralizing antibody Neutralizing biology virus diseases Biological Sciences Foodborne Illness Infectious Diseases Capsid Host-Pathogen Interactions Antibody Infection Protein Binding Biotechnology medicine.drug_class Immunology Virus Attachment Monoclonal antibody Microbiology Virus Antibodies Astrovirus Vaccine Related Structure-Activity Relationship Antigen Biodefense Virology medicine Humans neutralizing antibodies Amino Acid Sequence Agricultural and Veterinary Sciences Structure and Assembly Prevention Molecular protein structure-function biology.organism_classification Antibodies Neutralizing Emerging Infectious Diseases Insect Science biology.protein Capsid Proteins Immunization Digestive Diseases Mamastrovirus |
| Zdroj: | Journal of virology, vol 96, iss 1 Journal of Virology |
| Popis: | Human astrovirus is an important cause of viral gastroenteritis worldwide. Young children, the elderly, and the immunocompromised are especially at risk for contracting severe disease. However, no vaccines exist to combat human astrovirus infection. Evidence points to the importance of antibodies in protecting healthy adults from reinfection. To develop an effective subunit vaccine that broadly protects against diverse astrovirus serotypes, we must understand how neutralizing antibodies target the capsid surface at the molecular level. Here, we report the structures of the human astrovirus capsid spike domain bound to two neutralizing monoclonal antibodies. These antibodies bind two distinct conformational epitopes on the spike surface. We add to existing evidence that the human astrovirus capsid spike contains a receptor-binding domain and demonstrate that both antibodies neutralize human astrovirus by blocking virus attachment to host cells. We identify patches of conserved amino acids which overlap or border the antibody epitopes and may constitute a receptor-binding site. Our findings provide a basis for developing therapies to prevent and treat human astrovirus gastroenteritis. IMPORTANCE Human astroviruses infect nearly every person in the world during childhood and cause diarrhea, vomiting, and fever. Despite the prevalence of this virus, little is known about how antibodies block astrovirus infection. Here, we determined the crystal structures of the astrovirus capsid protein in complex with two virus-neutralizing antibodies. We show that the antibodies bind to two distinct sites on the capsid spike domain, however, both antibodies block virus attachment to human cells. Importantly, our findings support the use of the human astrovirus capsid spike as an antigen in a subunit-based vaccine to prevent astrovirus disease. |
| Databáze: | OpenAIRE |
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