Giuseppe
Emeritus
[Source: PLoS ONE, full text: (LINK). Abstract, edited.]
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Characterization of the 2009 Pandemic A/Beijing/501/2009 H1N1 Influenza Strain in Human Airway Epithelial Cells and Ferrets
Penghui Yang<SUP>1</SUP><SUP>,</SUP><SUP>3</SUP><SUP>#</SUP>, Jiejie Deng<SUP>2</SUP><SUP>#</SUP>, Chenggang Li<SUP>2</SUP><SUP>#</SUP>, Peirui Zhang<SUP>3</SUP><SUP>#</SUP>, Li Xing<SUP>1</SUP>, Zhiwei Li<SUP>3</SUP>, Wei Wang<SUP>2</SUP>, Yan Zhao<SUP>2</SUP>, Yiwu Yan<SUP>2</SUP>, Hongjing Gu<SUP>1</SUP>, Xin Liu<SUP>1</SUP>, Zhongpeng Zhao<SUP>1</SUP>, Shaogeng Zhang<SUP>3</SUP><SUP>*</SUP>, Xiliang Wang<SUP>1</SUP><SUP>*</SUP>, Chengyu Jiang<SUP>2</SUP><SUP>*</SUP>
<SUP></SUP>
1 Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, Beijing, China, 2 State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Peking Union Medical College, Tsinghua University; Chinese Academy of Medical Sciences, Beijing, China, 3 Department of Hepatobiliary, 302 Military Hospital, Beijing, China
Abstract
Background
A 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 Finding
In 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/Significance
Our 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.
Citation: Yang P, Deng J, Li C, Zhang P, Xing L, et al. (2012) Characterization of the 2009 Pandemic A/Beijing/501/2009 H1N1 Influenza Strain in Human Airway Epithelial Cells and Ferrets. PLoS ONE 7(9): e46184. doi:10.1371/journal.pone.0046184
Editor: Malcolm Gracie Semple, University of Liverpool, United Kingdom
Received: March 14, 2012; Accepted: August 29, 2012; Published: September 26, 2012
Copyright: ? 2012 Yang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The study was supported by the National Natural Scientific Foundation (30800977 and 30972614), the Beijing Natural Science Foundation (7112105), the National Basic Research Program (973) (2009CB522102 and 2012CB518905), and the National Key Technologies R&D Program (2006AA02Z450 and SS2012AA020905). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
* E-mail: Zhsg302@hotmail.com (SZ); chengyujiang@gmail.com (CJ); xiliangw@126.com (XW)
# These authors contributed equally to this work.
-Penghui Yang<SUP>1</SUP><SUP>,</SUP><SUP>3</SUP><SUP>#</SUP>, Jiejie Deng<SUP>2</SUP><SUP>#</SUP>, Chenggang Li<SUP>2</SUP><SUP>#</SUP>, Peirui Zhang<SUP>3</SUP><SUP>#</SUP>, Li Xing<SUP>1</SUP>, Zhiwei Li<SUP>3</SUP>, Wei Wang<SUP>2</SUP>, Yan Zhao<SUP>2</SUP>, Yiwu Yan<SUP>2</SUP>, Hongjing Gu<SUP>1</SUP>, Xin Liu<SUP>1</SUP>, Zhongpeng Zhao<SUP>1</SUP>, Shaogeng Zhang<SUP>3</SUP><SUP>*</SUP>, Xiliang Wang<SUP>1</SUP><SUP>*</SUP>, Chengyu Jiang<SUP>2</SUP><SUP>*</SUP>
<SUP></SUP>
1 Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, Beijing, China, 2 State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Peking Union Medical College, Tsinghua University; Chinese Academy of Medical Sciences, Beijing, China, 3 Department of Hepatobiliary, 302 Military Hospital, Beijing, China
Abstract
Background
A 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 Finding
In 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/Significance
Our 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.
Citation: Yang P, Deng J, Li C, Zhang P, Xing L, et al. (2012) Characterization of the 2009 Pandemic A/Beijing/501/2009 H1N1 Influenza Strain in Human Airway Epithelial Cells and Ferrets. PLoS ONE 7(9): e46184. doi:10.1371/journal.pone.0046184
Editor: Malcolm Gracie Semple, University of Liverpool, United Kingdom
Received: March 14, 2012; Accepted: August 29, 2012; Published: September 26, 2012
Copyright: ? 2012 Yang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The study was supported by the National Natural Scientific Foundation (30800977 and 30972614), the Beijing Natural Science Foundation (7112105), the National Basic Research Program (973) (2009CB522102 and 2012CB518905), and the National Key Technologies R&D Program (2006AA02Z450 and SS2012AA020905). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
* E-mail: Zhsg302@hotmail.com (SZ); chengyujiang@gmail.com (CJ); xiliangw@126.com (XW)
# These authors contributed equally to this work.
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