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Mediators of Inflammation
Volume 2018, Article ID 3586132, 12 pages
Research Article

Critical Role of HAX-1 in Promoting Avian Influenza Virus Replication in Lung Epithelial Cells

1Medical School and the Jiangsu Provincial Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, China
2Department of Veterinary Biomedical Sciences, College of Veterinary Medicine, University of Minnesota Twin Cities, St. Paul, MN 55108, USA
3College of Biological Sciences, Nanjing University, Nanjing, China

Correspondence should be addressed to Yongchun Song; nc.ude.ujn@hcygnos and Zheng Xing; ude.nmu@gnixz

Received 28 April 2017; Revised 21 August 2017; Accepted 17 September 2017; Published 16 January 2018

Academic Editor: Vinod K. Mishra

Copyright © 2018 Xue Li et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The PB1-F2 protein of influenza A virus has been considered a virulence factor, but its function in inducing apoptosis may be of disadvantage to viral replication. Host mechanisms to regulate PB1-F2-induced apoptosis remain unknown. We generated a PB1-F2-deficient avian influenza virus (AIV) H9N2 and found that the mutant virus replicated less efficiently in human lung epithelial cells. The PB1-F2-deficient virus produced less apoptotic cells, indicating that PB1-F2 of the H9N2 virus promotes apoptosis, occurring at the early stage of infection, in the lung epithelial cells. To understand how host cells regulate PB1-F2-induced apoptosis, we explored to identify cellular proteins interacting with PB1-F2 and found that HCLS1-associated protein X-1 (HAX-1), located mainly in the mitochondria as an apoptotic inhibitor, interacted with PB1-F2. Increased procaspase-9 activations, induced by PB1-F2, could be suppressed by HAX-1. In HAX-1 knockdown A549 cells, the replication of AIV H9N2 was suppressed in parallel to the activation of caspase-3 activation, which increased at the early stage of infection. We hypothesize that HAX-1 promotes AIV replication by interacting with PB1-F2, resulting in the suppression of apoptosis, prolonged cell survival, and enhancement of viral replication. Our data suggest that HAX-1 may be a promoting factor for AIV H9N2 replication through desensitizing PB1-F2 from its apoptotic induction in human lung epithelial cells.