Antigenic cartography reveals complexities of genetic determinants that lead to antigenic differences among pandemic GII.4 noroviruses
| Autor: | Joseph A Kendra, Gabriel I. Parra, Kentaro Tohma, Cara J. Lepore, Lauren A. Ford-Siltz |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
viruses 030106 microbiology Biology Antibodies Viral medicine.disease_cause Microbiology Genetic analysis Neutralization Herd immunity 03 medical and health sciences fluids and secretions Antigen antigenic mapping Pandemic Genotype medicine Humans Antigens Viral Pandemics Caliciviridae Infections Multidisciplinary pandemic Norovirus Structural protein virus diseases Biological Sciences Antigenic Variation Gastroenteritis GII.4 noroviruses 030104 developmental biology Amino Acid Substitution Capsid Proteins Binding Sites Antibody antigenic cartography Cartography |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.2015874118 |
| Popis: | Significance The GII.4 genotype of human noroviruses accounts for the majority of gastroenteritis outbreaks worldwide. This predominance is characterized by the chronological emergence of new variants in response to immune pressure. We performed a comprehensive analysis on a large panel of GII.4 viruses to investigate the genetic determinants of antigenic diversification. Using immunoassays and neutralization data, we observed major changes to antigenic properties over the course of GII.4 evolution and increased intervariant cross-reactivity across contemporary viruses. Antigenic cartography and sequence analyses indicated a minimum number of coevolving amino acid changes on the structural protein necessary for the emergence of antigenically distinct variants. These insights could facilitate the monitoring and characterization of emerging GII.4 noroviruses and the development of cross-protective vaccines. Noroviruses are the predominant cause of acute gastroenteritis, with a single genotype (GII.4) responsible for the majority of infections. This prevalence is characterized by the periodic emergence of new variants that present substitutions at antigenic sites of the major structural protein (VP1), facilitating escape from herd immunity. Notably, the contribution of intravariant mutations to changes in antigenic properties is unknown. We performed a comprehensive antigenic analysis on a virus-like particle panel representing major chronological GII.4 variants to investigate diversification at the inter- and intravariant level. Immunoassays, neutralization data, and cartography analyses showed antigenic similarities between phylogenetically related variants, with major switches to antigenic properties observed over the evolution of GII.4 variants. Genetic analysis indicated that multiple coevolving amino acid changes—primarily at antigenic sites—are associated with the antigenic diversification of GII.4 variants. These data highlight complexities of the genetic determinants and provide a framework for the antigenic characterization of emerging GII.4 noroviruses. |
| Databáze: | OpenAIRE |
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