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

14 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

Publisher Copyright:
© 2018 Xue Li et al.


Dive into the research topics of 'Critical Role of HAX-1 in Promoting Avian Influenza Virus Replication in Lung Epithelial Cells'. Together they form a unique fingerprint.

Cite this