Highly pathogenic avian influenza A virus H5N1 non-structural protein 1 is associated with apoptotic activation of the intrinsic mitochondrial pathway

Bian, Qian; Lu, Jing; Zhang, Li; Chi, Ying; Li, Yan; Guo, Hongxiong

Although Zhang et al (10) demonstrated that the H5N1 NS1 protein induced caspase-dependent apoptosis in human alveolar basal epithelial cells, Neuman et al (20) revealed that the activation of caspase is the common end event during apoptosis. Therefore, the study by Zhang et al (10) did not have enough evidence to support that the NS1 of H5N1 induced apoptosis through an extrinsic pathway. In the present study, the efficiency of NS1 in inducing apoptosis is lower than that of STS, however, the increasing synergistic effect on inducing apoptosis between STS and NS1 were observed. In addition, in the present study, the plasmid with the NS1 gene was transfected with Lipofectamine 2000 and the transfecting efficiency was lower than the penetrating ability of STS. At this point, although the capacity of inducing apoptosis of NS1 is weaker than STS in the present study, the importance of each one needs to be investigated further. Previous studies have revealed that the NS1 protein of influenza A viruses is a multifunctional viral protein that modulates the virus replication cycle and viral protein synthesis, and HA and neuropilin-1 (NP1) of H5N1 also induce apoptosis of airway epithelial cells (26, 27) . In vivo, there is a need to determine whether the synergetic effect on inducing apoptosis by NP1, nucleoprotein and HA exists. In particular, these proteins induce apoptosis by either sharing the same pathway or not.