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

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.

MicroRNA Expression Profile of Mouse Lung Infected with 2009 Pandemic H1N1 Influenza Virus

“…The virus strains used in this study included influenza virus A/Beijing/501/2009 (H1N1), an influenza virus isolated from a confirmed H1N1 influenza case in Beijing during 2009 [26,27], and A/Puerto Rico/8/34 (H1N1), a well characterized and mouse-adapted laboratory strain of influenza virus used as the genetic backbone for viruses from which inactivated influenza virus vaccines are generated. The A/Beijing/501/2009 H1N1 virus does not carry the D222G mutation reported in some H1N1 pandemic strains.…”

NS Segment of a 1918 Influenza A Virus-Descendent Enhances Replication of H1N1pdm09 and Virus-Induced Cellular Immune Response in Mammalian and Avian Systems

“…Since different studies have reported that H1N1pdm09 can induce apoptosis in late, but not in early stage of viral replication ( Yang et al, 2011 , 2012 ), we assessed the ability of the NS reassortants Gi-NS-PR8 and Gi-NS-Vict to induce late stage apoptosis (10 h p.i.) in A549 cells compared to Gi-wt.…”

The roles of apoptosis, autophagy and unfolded protein response in arbovirus, influenza virus, and HIV infections

“…Influenza virus NS1 protein interacts with β-tubulin, which arrests the infected cells in G2/M phase and affects Bcl-2 phosphorylation [290,291]. This, in turn, activates NFk B and induces INF-α and INF-β [292], which then induce the apoptosis cascade by induction of SOCS-3 expression [293,294]. Shiozaki et al, showed the cellular pro-apoptotic protein Siva-1 in A549 cells was involved in IAV replication through caspase activation [295].…”

“…Clusterin, a host protein, attenuates IAV NP-induced apoptosis and IAV replication [296]. Yang et al demonstrated that 2009 pandemic H1N1 A/Beijing/501/2009 could induce caspase-3-dependent apoptosis in the A549 cell line [292]. Husain and Harrod showed that caspase-3-mediated histone deacetylase 6 (HDAC6) cleavage in IAV-infected MDCK cells caused further damage in these cells [297].…”