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

Penghui Yang,Chenggang Li,Hongjing Gu,Yan Zhao,Wei Wang,Xin Liu,Yiwu Yan,Zhongpeng Zhao,Xiliang Wang,Chengyu Jiang,Peirui Zhang,Zhiwei Li,Shaogeng Zhang,Jiejie Deng,Li Xing,Malcolm Gracie Semple

doi:10.1371/journal.pone.0046184

Abstract

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.

Highlights

In April 2009, an outbreak of influenza in North American was found to be caused by a new swine-origin influenza A (H1N1) virus that has since become prevalent in human populations and has spread worldwide [1,2,3]
A549 cells were infected with A/Beijing/501 H1N1, a virus strain that emerged in Beijing, and the resulting cytotoxicity was compared with the toxicity induced by the A/California/07/2009 H1N1 virus strain and a seasonal H1N1 strain
In A549 cells, we found A/ Beijing/501 H1N1 virus exhibited high replication rate from 3 h post-infection; in contrast, California/07/2009 virus (CA07) virus did not produce significant levels of viral titers (Figure S1)

Summary

Introduction

In April 2009, an outbreak of influenza in North American was found to be caused by a new swine-origin influenza A (H1N1) virus that has since become prevalent in human populations and has spread worldwide [1,2,3]. Several publications have emphasized the possibility of the reassortment of the 2009 A (H1N1) influenza virus, A/H5N1 viruses or seasonal influenza viruses in humans and the potential serious implications for public health [4,5]. This 2009 pandemic H1N1 virus can cause human respiratory disease, but its pathogenesis remains poorly understood. The pathogenesis of this virus in human airway epithelial cells and mammals is not well understood

Methods

Results

Conclusion