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Identification of Potential Virulence Determinants associated H9N2 Avian Influenza Virus PB2 E627K Mutation by Comparative Proteomics

tetano

Editor, Senior Moderator
Proteomics. 2015 Jan 16. doi: 10.1002/pmic.201400309. [Epub ahead of print]
[h=1]Identification of Potential Virulence Determinants associated H9N2 Avian Influenza Virus PB2 E627K Mutation by Comparative Proteomics.[/h] Qi W[SUP]1[/SUP], Tian J, Su S, Huang L, Li H, Liao M.
[h=3]Author information[/h]

[h=3]Abstract[/h] Some highly pathogenic H5N1, H7N9 and H10N8 isolated from China carried six internal genes from H9N2 AIVs, and the key amino acids at 627 in PB2 of these viruses had mutated to K. To investigate the mechanism of increased pathogenicity for H9N2 AIV PB2 627K, we analyzed the difference in mouse lung proteins expression response to PB2 K627E. By iTRAQ method, we found that the mutated K627E contributed to a set of differentially expressed lung proteins, including five upregulated proteins and nine downregulated proteins at 12 h post infection; ten upregulated proteins and twenty five downregulated proteins at 72 h post infection. These proteins were chiefly involved within the cytoskeleton and motor proteins, antiviral proteins, regulation of glucocorticoids signal-associated proteins, pro- and anti-inflammatory proteins. Alteration of moesin, FKBP4, Hsp70, ezrin and sp-A may play important roles in increasing virulence and decreasing lungs antiviral response. Further, three upregulated proteins (moesin, ezrin and sp-A) caused by PB2 K627E were also confirmed in A549 cells. Moreover, overexpression of sp-A in A549 inhibited virus replication and downregulation promoted virus replication. In this study, sp-A as a potential virulence determinant associated H9N2 AIV PB2 E627K mutation was identified using comparative proteomics. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.


[h=4]KEYWORDS:[/h] Comparative proteomics; PB2 627K; Virulence determinant; iTRAQ; sp-A

PMID: 25641917 [PubMed - as supplied by publisher]
 
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