Mutations in haemagglutinin that affect receptor binding and pH stability increase replication of a PR8 influenza virus with H5 HA in the upper respiratory tract of ferrets and may contribute to transmissibility
| Autor: | Eleonora Molesti, Holly Shelton, Nigel J. Temperton, Wendy S. Barclay, Kim L. Roberts |
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| Rok vydání: | 2013 |
| Předmět: |
RNA viruses
Virus genetics Respiratory System Hemagglutinin Glycoproteins Influenza Virus Biology medicine.disease_cause Virus Replication Virus Microbiology 03 medical and health sciences Virology Influenza Human Influenza A virus medicine Animals Humans Viral shedding 030304 developmental biology 0303 health sciences Attenuated vaccine Influenza A Virus H5N1 Subtype 030306 microbiology Protein Stability Animal Ferrets virus diseases Viral membrane Hydrogen-Ion Concentration Influenza A virus subtype H5N1 Standard 3. Good health Virus Shedding Disease Models Animal Viral replication Mutation Receptors Virus Female Protein Binding |
| Zdroj: | The Journal of General Virology |
| ISSN: | 1465-2099 |
| Popis: | The H5N1 influenza A viruses have circulated widely in the avian population for 10 years with only sporadic infection of humans observed and no sustained human to human transmission. Vaccination against potential pandemic strains is one strategy in planning for future influenza pandemics; however, the success of live attenuated vaccines for H5N1 has been limited, due to poor replication in the human upper respiratory tract (URT). Mutations that increase the ability of H5N1 viruses to replicate in the URT will aid immunogenicity of these vaccines and provide information about humanizing adaptations in H5N1 strains that may signal transmissibility. As well as mediating receptor interactions, the haemagglutinin (HA) protein of influenza facilitates fusion of the viral membrane and genome entry into the host cell; this process is pH dependent. We have shown in this study that the pH at which a panel of avian influenza HA proteins, including H5, mediate fusion is higher than that for human influenza HA proteins, and that mutations in the H5 HA can reduce the pH of fusion. Coupled with receptor switching mutations, increasing the pH stability of the H5 HA resulted in increased viral shedding of H5N1 from the nasal cavity of ferrets and contact transmission to a co-housed animal. Ferret serum antibodies induced by infection with any of the mutated H5 HA viruses neutralized HA pseudotyped lentiviruses bearing homologous or heterologous H5 HAs, suggesting that this strategy to increase nasal replication of a vaccine virus would not compromise vaccine efficacy. |
| Databáze: | OpenAIRE |
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