tetano
Editor, Senior Moderator
J Virol. 2015 Feb 11. pii: JVI.03095-14. [Epub ahead of print]
[h=1]A(H7N9) virus results in early induction of proinflammatory cytokine responses in both human lung epithelial and endothelial cells and shows increased human adaption compared with avian H5N1 virus.[/h] Zeng H[SUP]1[/SUP], Belser JA[SUP]1[/SUP], Goldsmith CS[SUP]2[/SUP], Gustin KM[SUP]1[/SUP], Veguilla V[SUP]1[/SUP], Katz JM[SUP]1[/SUP], Tumpey TM[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Similar to H5N1 viruses, A(H7N9) influenza viruses have been associated with severe respiratory disease and fatal outcomes in humans. While high viral load, hypercytokinemia, and pulmonary endothelial cell involvement are known to be hallmarks of H5N1 virus infection, the pathogenic mechanism of the A(H7N9) virus in humans is largely unknown. Here, we assessed the ability of A(H7N9) virus to infect, replicate, and elicit innate immune responses in both human bronchial epithelial cells and pulmonary microvascular endothelial cells, compared with seasonal H3N2, avian H7N9, and H5N1 viruses. In epithelial cells, A(H7N9) virus replicated efficiently, but did not elicit robust induction of cytokines like that observed for H5N1 virus. In pulmonary endothelial cells, A(H7N9) virus efficiently initiated infection, however, no released infectious virus was detected. The magnitude of induction of host cytokine responses was comparable between A(H7N9) and H5N1 virus infection. Additionally, we utilized differentiated human primary bronchial/tracheal epithelial cells to investigate cellular tropism using transmission electron microscopy and the impact of temperature on virus replication. Interestingly, A(H7N9) virus budded from the surface of both ciliated and mucin-secretory cells. Furthermore, A(H7N9) virus replicated to a significantly higher titer at 37?C than at 33?C, with improved replication capacity at 33?C compared to H5N1 virus. These findings suggest that a high viral load from lung epithelial cells, coupled with induction of host responses in endothelial cells may contribute to the severe pulmonary disease observed following H7N9 virus infection. Improved adaption of A(H7N9) virus to human upper airway poses an important threat to public health.
[h=4]IMPORTANCE:[/h] A(H7N9) influenza viruses have caused over 400 documented human infections with a 30% fatality rate since early 2013. However, these novel viruses lack many molecular determinants previously identified with mammalian pathogenicity, necessitating a closer examination of how these viruses elicit host responses which could be detrimental. This study provides greater insight into the interaction of this virus with host lung epithelial cells and endothelial cells, which results in high viral load, epithelial cell death, and elevated immune response in lung, revealing the mechanism of pathogenesis and disease development among A(H7N9)-infected patients. In particular, we characterized the involvement of pulmonary endothelial cells, a cell type in the human lung accessible to influenza virus following damage of the epithelial monolayer, and its potential role in the development of severe pneumonia caused by A(H7N9) infection in humans.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.
PMID: 25673714 [PubMed - as supplied by publisher]
[h=1]A(H7N9) virus results in early induction of proinflammatory cytokine responses in both human lung epithelial and endothelial cells and shows increased human adaption compared with avian H5N1 virus.[/h] Zeng H[SUP]1[/SUP], Belser JA[SUP]1[/SUP], Goldsmith CS[SUP]2[/SUP], Gustin KM[SUP]1[/SUP], Veguilla V[SUP]1[/SUP], Katz JM[SUP]1[/SUP], Tumpey TM[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Similar to H5N1 viruses, A(H7N9) influenza viruses have been associated with severe respiratory disease and fatal outcomes in humans. While high viral load, hypercytokinemia, and pulmonary endothelial cell involvement are known to be hallmarks of H5N1 virus infection, the pathogenic mechanism of the A(H7N9) virus in humans is largely unknown. Here, we assessed the ability of A(H7N9) virus to infect, replicate, and elicit innate immune responses in both human bronchial epithelial cells and pulmonary microvascular endothelial cells, compared with seasonal H3N2, avian H7N9, and H5N1 viruses. In epithelial cells, A(H7N9) virus replicated efficiently, but did not elicit robust induction of cytokines like that observed for H5N1 virus. In pulmonary endothelial cells, A(H7N9) virus efficiently initiated infection, however, no released infectious virus was detected. The magnitude of induction of host cytokine responses was comparable between A(H7N9) and H5N1 virus infection. Additionally, we utilized differentiated human primary bronchial/tracheal epithelial cells to investigate cellular tropism using transmission electron microscopy and the impact of temperature on virus replication. Interestingly, A(H7N9) virus budded from the surface of both ciliated and mucin-secretory cells. Furthermore, A(H7N9) virus replicated to a significantly higher titer at 37?C than at 33?C, with improved replication capacity at 33?C compared to H5N1 virus. These findings suggest that a high viral load from lung epithelial cells, coupled with induction of host responses in endothelial cells may contribute to the severe pulmonary disease observed following H7N9 virus infection. Improved adaption of A(H7N9) virus to human upper airway poses an important threat to public health.
[h=4]IMPORTANCE:[/h] A(H7N9) influenza viruses have caused over 400 documented human infections with a 30% fatality rate since early 2013. However, these novel viruses lack many molecular determinants previously identified with mammalian pathogenicity, necessitating a closer examination of how these viruses elicit host responses which could be detrimental. This study provides greater insight into the interaction of this virus with host lung epithelial cells and endothelial cells, which results in high viral load, epithelial cell death, and elevated immune response in lung, revealing the mechanism of pathogenesis and disease development among A(H7N9)-infected patients. In particular, we characterized the involvement of pulmonary endothelial cells, a cell type in the human lung accessible to influenza virus following damage of the epithelial monolayer, and its potential role in the development of severe pneumonia caused by A(H7N9) infection in humans.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.
PMID: 25673714 [PubMed - as supplied by publisher]