The 2009 pandemic A/Wenshan/01/2009 H1N1 induces apoptotic cell death in human airway epithelial cells

Yang, Ning; Hong, Xiaowei; Yang, Peng; Ju, Xiangwu; Wang, Yuguo; Tang, Jun; Li, Chenggang; Fan, Quanshui; Zhang, Fuqiang; Chen, Zhongwei; Li, Xing; Zhao, Zhongpeng; Gao, Xiao; Liao, Guoyang; Li, Qihan; Wang, Xiliang; Li, Dangsheng; Jiang, Chengyu

doi:10.1093/jmcb/mjr017

Cited by 26 publications

(23 citation statements)

References 42 publications

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“…The anti-apoptotic properties are favorable for the early life-cycle of the virus, which is reminiscent of the effect of anti-apoptotic proteins on respiratory syncytial virus infection (Othumpangat et al, 2012). Induction of apoptosis by influenza virus has been reported in numerous cells both in vitro (Roulston et al, 1999) and in vivo (Yang et al, 2011). Interaction of the NS1 protein with β -tubulin in cells infected with influenza disrupted cell division and induced apoptosis in A549 cells (Han et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Expression of non-structural-1A binding protein in lung epithelial cells is modulated by miRNA-548an on exposure to influenza A virus

et al. 2013

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Understanding the host response to influenza A virus infection is essential for developing intervention approaches. We show that infection of human alveolar epithelial cells and human bronchial epithelial cells with influenza A for 3 h resulted in down-regulation of host hsa-miRNA-548an (miRNA-548an) which triggered the overexpression of influenza non-structural-1A binding protein (IVNS1ABP, herein referred to as NS1ABP). Reduced NS1ABP mRNA and NS1ABP protein expression after transfection of miRNA-548an mimic or increased NS1ABP mRNA and NS1ABP protein expression after transfection of miRNA-548an inhibitor provided evidence that miRNA-548an is involved in the regulation of NS1ABP. Transfection of cells with inhibitor led to reduced apoptosis of infected cells while transfection of mimic led to increased apoptosis and reduced influenza copy number suggesting that NS1ABP has a role in viral maintenance. Thus, miRNA-548an may be an important target in controlling the early stage infection of influenza A.

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Section: Discussionmentioning

confidence: 99%

Expression of non-structural-1A binding protein in lung epithelial cells is modulated by miRNA-548an on exposure to influenza A virus

et al. 2013

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“…Influenza virus induces apoptosis in many cell types both in vivo and in vitro, to some extent, apoptosis is a protective response of host cell to virus infection [8], [24], [25], [26]. Our previous studies have firstly confirmed that the 2009 pandemic H1N1 A/Wenshan/01/2009 strain could induce apoptosis in human epithelial cell lines and the viral entry was mediated by clathirin-and dynamin-dependent endocytosis in CNE-2Z and A549 cell lines [7]. Here, we demonstrated that the 2009 pandemic H1N1 A/Beijing/501/2009 could induce caspase-3-dependent apoptosis in A549 cells and ferrets, which is likely to contribute to virus pathogenesis.…”

Section: Discussionmentioning

confidence: 96%

Characterization of the 2009 Pandemic A/Beijing/501/2009 H1N1 Influenza Strain in Human Airway Epithelial Cells and Ferrets

Yang

Deng

et al. 2012

PLoS ONE

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BackgroundA novel 2009 swine-origin influenza A H1N1 virus (S-OIV H1N1) has been transmitted among humans worldwide. However, the pathogenesis of this virus in human airway epithelial cells and mammals is not well understood.Methodology/Principal FindingIn this study, we showed that a 2009 A (H1N1) influenza virus strain, A/Beijing/501/2009, isolated from a human patient, caused typical influenza-like symptoms including weight loss, fluctuations in body temperature, and pulmonary pathological changes in ferrets. We demonstrated that the human lung adenocarcinoma epithelial cell line A549 was susceptible to infection and that the infected cells underwent apoptosis at 24 h post-infection. In contrast to the seasonal H1N1 influenza virus, the 2009 A (H1N1) influenza virus strain A/Beijing/501/2009 induced more cell death involving caspase-3-dependent apoptosis in A549 cells. Additionally, ferrets infected with the A/Beijing/501/2009 H1N1 virus strain exhibited increased body temperature, greater weight loss, and higher viral titers in the lungs. Therefore, the A/Beijing/501/2009 H1N1 isolate successfully infected the lungs of ferrets and caused more pathological lesions than the seasonal influenza virus. Our findings demonstrate that the difference in virulence of the 2009 pandemic H1N1 influenza virus and the seasonal H1N1 influenza virus in vitro and in vivo may have been mediated by different mechanisms.Conclusion/SignificanceOur understanding of the pathogenesis of the 2009 A (H1N1) influenza virus infection in both humans and animals is broadened by our findings that apoptotic cell death is involved in the cytopathic effect observed in vitro and that the pathological alterations in the lungs of S-OIV H1N1-infected ferrets are much more severe.

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“…Influenza viruses have been reported to induce apoptosis in numerous cell types, both in vivo [30], [31] and in vitro [32]. Several viral proteins (M1, NS1, and PB1-F2) from different strains of human influenza viruses have been shown to induce or inhibit apoptosis in human cells [33], [34], [35].…”

Section: Discussionmentioning

confidence: 99%

“…Several viral proteins (M1, NS1, and PB1-F2) from different strains of human influenza viruses have been shown to induce or inhibit apoptosis in human cells [33], [34], [35]. Ning Yang et al (2011) recently reported that the 2009 pandemic H1N1 strain, A/Wenshan/01/2009, induce apoptotic cell death in epithelial cells of the human respiratory tract [32]. Our results indicated that influenza virus A/Beijing/501/2009(H1N1) NS1 alone can induce apoptosis on A549 cells.…”

Section: Discussionmentioning

confidence: 99%

Influenza Virus A/Beijing/501/2009(H1N1) NS1 Interacts with β-Tubulin and Induces Disruption of the Microtubule Network and Apoptosis on A549 Cells

Han

Chen

et al. 2012

PLoS ONE

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NS1 of influenza A virus is a key multifunctional protein that plays various roles in regulating viral replication mechanisms, host innate/adaptive immune responses, and cellular signalling pathways. These functions rely on its ability to participate in a multitude of protein-protein and protein-RNA interactions. To gain further insight into the role of NS1, a tandem affinity purification (TAP) method was utilized to find unknown interaction partner of NS1. The protein complexes of NS1 and its interacting partner were purified from A549 cell using TAP-tagged NS1 as bait, and co-purified cellular factors were identified by mass spectrometry (MS). We identified cellular β-tubulin as a novel interaction partner of NS1. The RNA-binding domain of NS1 interacts with β-tubulin through its RNA-binding domain, as judged by a glutathione S-transferase (GST) pull-down assay with the GST-fused functional domains of NS1. Immunofluorescence analysis further revealed that NS1 with β-tubulin co-localized in the nucleus. In addition, the disruption of the microtubule network and apoptosis were also observed on NS1-transfected A549 cells. Our findings suggest that influenza A virus may utilize its NS1 protein to interact with cellular β-tubulin to further disrupt normal cell division and induce apoptosis. Future work will illustrate whether this interaction is uniquely specific to the 2009 pandemic H1N1 virus.

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The 2009 pandemic A/Wenshan/01/2009 H1N1 induces apoptotic cell death in human airway epithelial cells

Cited by 26 publications

References 42 publications

Expression of non-structural-1A binding protein in lung epithelial cells is modulated by miRNA-548an on exposure to influenza A virus

Expression of non-structural-1A binding protein in lung epithelial cells is modulated by miRNA-548an on exposure to influenza A virus

Characterization of the 2009 Pandemic A/Beijing/501/2009 H1N1 Influenza Strain in Human Airway Epithelial Cells and Ferrets

Influenza Virus A/Beijing/501/2009(H1N1) NS1 Interacts with β-Tubulin and Induces Disruption of the Microtubule Network and Apoptosis on A549 Cells

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