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

Xue Li, Bingqian Qu, Ganlin He, Carol J. Cardona, Yongchun Song, Zheng Xing

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


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.

Original languageEnglish (US)
Article number3586132
JournalMediators of inflammation
StatePublished - 2018

Bibliographical note

Funding Information:
This study was supported by the Minnesota Department of Agriculture Award (UMN Response to AI; Award nos. CON000000058786-00056110 and 00056111) to Zheng Xing and Carol J. Cardona and by the National Natural Science Foundation of China (Grant no. 81571993) to Zheng Xing. The authors thank Lin Ding at the University of Heidelberg, Germany, for providing the plasmid expressing HAX-1 and MitoTrack reagent.

Publisher Copyright:
© 2018 Xue Li et al.


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