A(H7N9) virus results in early induction of proinflammatory cytokine responses in both human lung epithelial and endothelial cells and shows increased human adaptation compared with avian H5N1 Virus

Academic Article

Abstract

  • 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. In this study, 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 the abilities of 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 magnitudes of induction of host cytokine responses were comparable between A(H7N9) and H5N1 virus infection. Additionally, we utilized differentiated human primary bronchial and 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 surfaces 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 that of 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 adaptation of A(H7N9) virus to human upper airway poses an important threat to public health.
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    Digital Object Identifier (doi)

    Author List

  • Zeng H; Belser JA; Goldsmith CS; Gustin KM; Veguilla V; Katz JM; Tumpey TM
  • Start Page

  • 4655
  • End Page

  • 4667
  • Volume

  • 89
  • Issue

  • 8