Front Microbiol. 2019 Mar 6;10:432. doi: 10.3389/fmicb.2019.00432. eCollection 2019.
Identification of Amino Acid Residues in Influenza A Virus PA-X That Contribute to Enhanced Shutoff Activity.
Oishi K1, Yamayoshi S1, Kawaoka Y1,2,3.
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Abstract
The influenza virus protein PA-X modulates the host immune responses and viral pathogenicity through suppression of host protein expression. The endonuclease active site in the N-terminal region, the basic amino acid cluster in the C-terminal PA-X-specific region, and N-terminal acetylation of PA-X by NatB are important for the shutoff activity of PA-X. Here, we focused on the shutoff activity of PA-X derived from the A/California/04/2009 and A/WSN/33 viruses because these two PA-X proteins differ in their shutoff activity. Mutagenesis analysis revealed that proline and serine at positions 28 and 65, respectively, play a central role in this difference. Furthermore, we found that P28 and S65 also affect the shutoff activity of PA-X derived from other influenza virus subtypes. These data demonstrate that P28 and S65 contribute to enhanced shutoff activity of PA-X.
KEYWORDS:
PA-X; influenza A virus; mRNA degradation; mutagenesis analysis; shutoff activity
PMID: 30894843 PMCID: PMC6414799 DOI: 10.3389/fmicb.2019.00432
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Identification of Amino Acid Residues in Influenza A Virus PA-X That Contribute to Enhanced Shutoff Activity.
Oishi K1, Yamayoshi S1, Kawaoka Y1,2,3.
Author information
Abstract
The influenza virus protein PA-X modulates the host immune responses and viral pathogenicity through suppression of host protein expression. The endonuclease active site in the N-terminal region, the basic amino acid cluster in the C-terminal PA-X-specific region, and N-terminal acetylation of PA-X by NatB are important for the shutoff activity of PA-X. Here, we focused on the shutoff activity of PA-X derived from the A/California/04/2009 and A/WSN/33 viruses because these two PA-X proteins differ in their shutoff activity. Mutagenesis analysis revealed that proline and serine at positions 28 and 65, respectively, play a central role in this difference. Furthermore, we found that P28 and S65 also affect the shutoff activity of PA-X derived from other influenza virus subtypes. These data demonstrate that P28 and S65 contribute to enhanced shutoff activity of PA-X.
KEYWORDS:
PA-X; influenza A virus; mRNA degradation; mutagenesis analysis; shutoff activity
PMID: 30894843 PMCID: PMC6414799 DOI: 10.3389/fmicb.2019.00432
Free full text