Twenty amino acids at the C-terminus of PA-X are associated with increased influenza A virus replication and pathogenicity.
J Gen Virol
; 96(8): 2036-2049, 2015 Aug.
Article
em En
| MEDLINE
| ID: mdl-25877935
ABSTRACT
The PA-X protein, arising from ribosomal frameshift during PA translation, was recently discovered in influenza A virus (IAV). The C-terminal domain 'X' of PA-X proteins in IAVs can be classified as full-length (61 aa) or truncated (41 aa). In the main, avian influenza viruses express full-length PA-X proteins, whilst 2009 pandemic H1N1 (pH1N1) influenza viruses harbour truncated PA proteins. The truncated form lacks aa 232-252 of the full-length PA-X protein. The significance of PA-X length in virus function remains unclear. To address this issue, we constructed a set of contemporary influenza viruses (pH1N1, avian H5N1 and H9N2) with full and truncated PA-X by reverse genetics to compare their replication and host pathogenicity. All full-length PA-X viruses in human A549 cells conferred 10- to 100-fold increase in viral replication and 5-8% increase in apoptosis relative to corresponding truncated PA-X viruses. Full-length PA-X viruses were more virulent and caused more severe inflammatory responses in mice. Furthermore, aa 233-252 at the C terminus of PA-X strongly suppressed co-transfected gene expression by â¼ 50%, suggesting that these terminal 20 aa could play a role in enhancing viral replication and contribute to virulence.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
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Replicação Viral
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Proteínas não Estruturais Virais
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Influenza Humana
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Vírus da Influenza A Subtipo H1N1
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Virus da Influenza A Subtipo H5N1
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Vírus da Influenza A Subtipo H9N2
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article