H7N9 Influenza A Virus Exhibits Importin-α7-Mediated Replication in the Mammalian Respiratory Tract

Am J Pathol. 2017 Apr;187(4):831-840. doi: 10.1016/j.ajpath.2016.12.017. Epub 2017 Feb 9.


The acute respiratory distress syndrome (ARDS) is the leading cause of death in influenza A virus (IAV)-infected patients. Hereby, the cellular importin-α7 gene plays a major role. It promotes viral replication in the lung, thereby increasing the risk for the development of pneumonia complicated by ARDS. Herein, we analyzed whether the recently emerged H7N9 avian IAV has already adapted to human importin-α7 use, which is associated with high-level virus replication in the mammalian lung. Using a cell-based viral polymerase activity assay, we could detect a decreased H7N9 IAV polymerase activity when importin-α7 was silenced by siRNA. Moreover, virus replication was diminished in the murine cells lacking the importin-α7 gene. Consistently, importin-α7 knockout mice presented reduced pulmonary virus titers and lung lesions as well as enhanced survival rates compared to wild-type mice. In summary, our results show that H7N9 IAV have acquired distinct features of adaptation to human host factors that enable enhanced virulence in mammals. In particular, adaptation to human importin-α7 mediates elevated virus replication in the mammalian lung, which might have contributed to ARDS observed in H7N9-infected patients.

MeSH terms

  • Animals
  • Chemokines / metabolism
  • Cytokines / metabolism
  • DNA-Directed DNA Polymerase / metabolism
  • Gene Deletion
  • HEK293 Cells
  • Humans
  • Inflammation Mediators / metabolism
  • Influenza A Virus, H7N9 Subtype / pathogenicity
  • Influenza A Virus, H7N9 Subtype / physiology*
  • Lung / metabolism
  • Lung / pathology
  • Lung / virology
  • Mammals / virology*
  • Mice
  • Respiratory System / metabolism*
  • Respiratory System / virology*
  • Virulence
  • Virus Replication*
  • alpha Karyopherins / genetics
  • alpha Karyopherins / metabolism*


  • Chemokines
  • Cytokines
  • Inflammation Mediators
  • alpha Karyopherins
  • DNA-Directed DNA Polymerase