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

The results of the present study indicate that the NS1 protein of the H5N1 highly pathogenic avian influenza A virus strain is associated with apoptotic activation of NCI-H1299 through the intrinsic mitochondrial pathway. The MTT assay and flow cytometric analysis revealed that the NS1 protein-induced apoptosis of NCI-H1299 cells and its activity may be enhanced by STS. Additionally, the NS1 protein together with STS was able to cause the release of cytochrome c from the mitochondria to the cytosol, and the change of MMP. During the intrinsic mitochondrial apoptosis process, the permeabilization of the mitochondrial outer membrane is the critical step, which results in the release of several apoptogenic factors from the intermembrane space of mitochondria (20) (21) (22) . Cytochrome c is one of these factors, which binds to the adaptor apoptotic peptidase-activating factor 1 that subsequently recruits cytosolic pro-caspase-9 into a heptameric apoptosome (23) . The intrinsic mitochondrial apoptosis pathway is one of the major pathways during viral pathogenesis that include human immunodeficiency virus and severe acute respiratory syndrome coronavirus (24, 25) .