Characterization of the 2009 pandemic A/Beijing/501/2009 H1N1 influenza strain in human airway epithelial cells and ferrets.
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.


RESULTS
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.


CONCLUSIONS
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.
Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, Beijing, China.
Penghui
P
Yang
Jiejie
J
Deng
Chenggang
C
Li
Peirui
P
Zhang
Li
L
Xing
Zhiwei
Z
Li
Wei
W
Wang
Yan
Y
Zhao
Yiwu
Y
Yan
Hongjing
H
Gu
Xin
X
Liu
Zhongpeng
Z
Zhao
Shaogeng
S
Zhang
Xiliang
X
Wang
Chengyu
C
Jiang
D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000821:virology*; D005260:Female; D005289:Ferrets / Q000821:virology; D006801:Humans; D020287:In Situ Nick-End Labeling; D053118:Influenza A Virus, H1N1 Subtype / Q000145:classification / Q000235:genetics; D007251:Influenza, Human; D008297:Male; D058873:Pandemics; D012137:Respiratory System / Q000821:virology*