Occurrence of oxidative stress is common in influenza, and renders the host more susceptible to pathogenic effects including cell death. We previously reported that down-regulation of superoxide anion dismutase 1 (SOD1) by influenza A virus (IAV) resulted in a significant increase in the levels of reactive oxygen species (ROS) and viral PB1 polymerase gene product in the early stage of infection. However, the precise molecular mechanism of IAV-mediated ROS generation is not yet fully understood. In this study, we investigated the possible involvement of the key virulence factor PB1-F2 in ROS generation and its contribution to the viral propagation and cell death. The key virulence factor PB1-F2 was found to be responsible, at least in part, for the ROS generation through lowering the SOD1 level in alveolar epithelial A549 cells. PB1-F2 overexpression resulted in SOD1 diminishment and ROS enhancement, while another virulent factor, NS1, did not show significant changes. Inversely, we examined the effects of the absence of PB1-F2 using mutant IAV lacking PB1-F2 expression (mutantΔF2). Infection with mutantΔF2 virus did not significantly lower the SOD1 level, and thus generated moderately low levels of ROS. In addition, the oxidative activity of PB1-F2 was directly reflected by cell viability and death. Infection with the mutant virus reduced the percentage of apoptotic cells more than two-fold compared to the wild-type IAV in A549 cells. Furthermore, expression of exogenous SOD1 gene abrogated a large portion of the PB1-F2-induced apoptosis of cells infected with wild-type IAV, but affected much less of the mutantΔF2 virus-infected cells. These results suggest that the PB1-F2 is directly implicated in virus-induced oxidative stress, thereby contributing to the early stages of IAV replication cycle and ultimately to disease severity.
|Number of pages||7|
|Journal||Biochemical and Biophysical Research Communications|
|Publication status||Published - 2015 Apr 17|
- Influenza A virus
- Superoxide anion dismutase 1
ASJC Scopus subject areas