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

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

doi:10.1186/1743-422x-7-51

Abstract

BackgroundIt 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.ResultsNS1 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.ConclusionsInfluenza 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.

Highlights

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
The apoptosis was observed among the alveolar epithelial cells of two patients who died of H5N1 infection, suggesting a possible role of apoptosis in H5N1 pathogenesis in humans [13]
The NS1 proteins derived from H5N9 or H5N1 could induce apoptosis in MDCK, HeLa cells or human airway epithelial cells [8,24]; in sharp contrast, the NS1 proteins from H1N1 or H3N2 were reported to downregulate apoptosis in MDCK and Vero cells [18,25]

Summary

Introduction

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. The multifunctional NS1 protein is widely considered as a virulence factor and contributes significantly disease pathogenesis by modulating a number of virus and host-cell processes [19,20,21,22]. It is possible that these diverse observations might be resulted from the differences of virus subtypes and strains, as well as the host cell system being used, highlighting that further characterization of the NS1 protein and its mechanism involved in the induction of apoptosis is highly essential for understanding the pathogenesis of influenza

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