Residues F103 and M106 within the influenza A virus NS1 CPSF4-binding region regulate interferon-stimulated gene translation initiation.
Virology
; 508: 170-179, 2017 08.
Article
em En
| MEDLINE
| ID: mdl-28554059
ABSTRACT
Influenza A virus (IAV) non-structural protein 1 (NS1) suppresses host innate immune responses by inhibiting type I interferon (IFN) production. We provide evidence that residues F103 and M106 in the CPSF4-binding domain of A/HK/1/68 [H3N2] NS1 contribute to post-transcriptional inhibition of antiviral IFN-stimulated genes (ISGs), thereby suppressing an antiviral type I IFN response. Recombinant (r) IAVs encoding F103L and M106I mutations in NS1 replicate to significantly lower viral titers in human A549 lung epithelial cells and primary type II alveolar cells. In A549 cells, rIAVs encoding these mutant NS1s induce higher levels of IFN-ß production and are more sensitive to the antiviral effects of IFN-ß treatment. qPCR characterization of polysomal mRNA, in the presence or absence of IFN-ß treatment, identified a greater proportion of heavy polysome-associated ISGs including EIF2AK2, OAS1, and MxA in A549 cells infected with rIAVs encoding these CPSF4-binding mutant NS1s, in contrast to rIAV encoding wildtype NS1.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Iniciação Traducional da Cadeia Peptídica
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Interferons
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Proteínas não Estruturais Virais
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Fator de Especificidade de Clivagem e Poliadenilação
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Influenza Humana
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Vírus da Influenza A Subtipo H3N2
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Virology
Ano de publicação:
2017
Tipo de documento:
Article