Multiple HA substitutions in highly pathogenic avian influenza H5Nx viruses contributed to the change in the NA subtype preference.
Virulence
; 13(1): 990-1004, 2022 12.
Article
em En
| MEDLINE
| ID: mdl-36560870
ABSTRACT
Novel highly pathogenic avian influenza (HPAI) H5Nx viruses are predominantly circulating worldwide, with an increasing potential threat of an outbreak in humans. It remains largely unknown how the stably maintained HPAI H5N1 suddenly altered its neuraminidase (NA) to other NA subtypes, which resulted in the emergence and evolution of H5Nx viruses. Here, we found that a combination of four specific amino acid (AA) substitutions (S123P-T156A-D183N- S223 R) in the hemagglutinin (HA) protein consistently observed in the H5Nx markedly altered the NA preference of H5N1 viruses. These molecular changes in H5N1 impaired its fitness, particularly viral growth and the functional activities of the HA and NA proteins. Among the AA substitutions identified, the T156A substitution, which contributed to the NA shift, also dramatically altered the antigenicity of H5N1 viruses, suggesting an occurrence of antigenic drift triggered by selective pressure. Our study shows the importance of how HA and NA complement each other and that antigenic drift in HA can potentially cause a shift in the NA protein in influenza A virus evolution.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Vírus da Influenza A
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Virus da Influenza A Subtipo H5N1
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Influenza Aviária
Limite:
Animals
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Humans
Idioma:
En
Revista:
Virulence
Ano de publicação:
2022
Tipo de documento:
Article