Preventing an Antigenically Disruptive Mutation in Egg-Based H3N2 Seasonal Influenza Vaccines by Mutational Incompatibility
| Autor: | Chris Ka Pun Mok, Ian A. Wilson, Corwin M. Nycholat, Douglas C. Wu, Chih Wei Lin, Wilson W.S. Ng, Ryan McBride, Weiwen Liang, Rameshwar U. Kadam, Huibin Lv, Andrew J. Thompson, James C. Paulson, Nicholas C. Wu |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
epistasis
Antigenicity Virus Cultivation Protein Conformation Viral protein receptor binding Adaptation Biological Mutation Missense Hemagglutinin (influenza) Hemagglutinin Glycoproteins Influenza Virus Chick Embryo Biology Crystallography X-Ray medicine.disease_cause Microbiology Virus Article influenza virus 03 medical and health sciences 0302 clinical medicine Antigen Virology vaccine Influenza Human medicine Animals Technology Pharmaceutical Humans hemagglutinin Antigens Viral 030304 developmental biology 0303 health sciences Mutation Binding Sites Influenza A Virus H3N2 Subtype 3. Good health Influenza Vaccines egg-adaptive mutation antigenicity biology.protein Epistasis Parasitology Seasons Adaptation 030217 neurology & neurosurgery |
| Zdroj: | Cell Host & Microbe |
| ISSN: | 1934-6069 1931-3128 |
| Popis: | Summary Egg-based seasonal influenza vaccines are the major preventive countermeasure against influenza virus. However, their effectiveness can be compromised when antigenic changes arise from egg-adaptive mutations on influenza hemagglutinin (HA). The L194P mutation is commonly observed in egg-based H3N2 vaccine seed strains and significantly alters HA antigenicity. An approach to prevent L194P would therefore be beneficial. We show that emergence of L194P during egg passaging can be impeded by preexistence of a G186V mutation, revealing strong incompatibility between these mutations. X-ray structures illustrate that individual G186V and L194P mutations have opposing effects on the HA receptor-binding site (RBS), and when both G186V and L194P are present, the RBS is severely disrupted. Importantly, wild-type HA antigenicity is maintained with G186V, but not L194P. Our results demonstrate that these epistatic interactions can be used to prevent the emergence of mutations that adversely alter antigenicity during egg adaptation. Graphical Abstract Highlights • Most H3N2 egg isolates carry hemagglutinin mutation G186V or L194P, but not both • Hemagglutinin double mutation G186V/L194P is highly deleterious to the virus • Hemagglutinin double mutation G186V/L194P disrupts the receptor-binding site • Wild-type hemagglutinin antigenicity is maintained in G186V, but not in L194P Wu et al. characterize the incompatibility between two major egg-adaptive mutations in human H3N2 virus hemagglutinin, G186V and L194P, which confer either minimal or significant antigenic change, respectively. This study suggests that the antigenically disruptive mutation L194P that occurs during egg-based influenza vaccine production can be prevented by mutational incompatibility. |
| Databáze: | OpenAIRE |
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