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. 2010 Mar 3:7:51.
doi: 10.1186/1743-422X-7-51.

Highly pathogenic avian influenza A virus H5N1 NS1 protein induces caspase-dependent apoptosis in human alveolar basal epithelial cells

Chuanfu Zhang  1 , Yutao Yang, Xiaowei Zhou, Xuelin Liu, Hongbin Song, Yuxian He, Peitang Huang
Affiliations

Highly pathogenic avian influenza A virus H5N1 NS1 protein induces caspase-dependent apoptosis in human alveolar basal epithelial cells

Chuanfu Zhang et al. Virol J. .

Abstract

Background: It is widely considered that the multifunctional NS1 protein of influenza A viruses contributes significantly disease pathogenesis by modulating a number of virus and host-cell processes, but it is highly controversial whether this non-structural protein is a proapoptotic or antiapoptotic factor in infected cells.

Results: NS1 protein of influenza A/chicken/Jilin/2003 virus, a highly pathogenic H5N1 strain, could induce apoptosis in the carcinomic human alveolar basal epithelial cells (A549) by electron microscopic and flow cytometric analyses. NS1 protein-triggered apoptosis in A549 cells is via caspase-dependent pathway.

Conclusions: Influenza A virus NS1 protein serves as a strong inducer of apoptosis in infected human respiratory epithelial cells and plays a critical role in disease pathogenesis.

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Figures

Figure 1
Figure 1
H5N1 NS1 protein induces apoptosis in A549 cells visualized by transmission electron microscopy. Normal cell (A) and transfected cell with pCMV-Myc empty vector (B) show that the nuclear shapes are intact. H5N1 NS1-transfected cell shows chromatins condensed, shrunk and aggregated along inside the nuclear membrane, and reveals the apoptotic bodies. (× 5,000).
Figure 2
Figure 2
Flow cytometric analysis of H5N1 NS-induced apoptosis. The dot plot diagrams represent typical apoptotic and necrotic cell populations detected by Annexin V-FITC and PI staining. A. A549 cells transfected with the empty PCMV-Myc vectors. B. A549 cells transfected with pCMV-Myc/NS1. The lower left quadrants of the panels show viable intact cells, which were negative for Annexin V-FITC binding and excluded PI staining (FITC-/PI-); the upper right quadrants show nonviable, necrotic cells, which were positive for Annexin V-FITC binding and PI uptake (FITC+/PI+). The lower right quadrants represent apoptotic cells, positive for Annexin V-FITC and negative for PI (FITC+/PI-).
Figure 3
Figure 3
Caspase-3 and caspase-9 activation in NS1-transfected A549 cells. The cells were transfected with the plasmid pCMV-Myc/NS1 for 0 h, 12 h, 24 h, and 48 h. Intracellular caspase-3 and caspase-9 activation were detected by Western blotting. The β-actin was used as a loading control.
Figure 4
Figure 4
Enzyme activities of caspase-3 and caspase-9 in NS1-transfected A549 cells. Enzyme activities were detected by Caspase-3/CPP32 Colorimetric Protease Assay and Caspase-9/Mch6 Colorimetric Assay, respectively.
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