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H7N9 Influenza A Virus Exhibits Importin-α7-Mediated Replication in the Mammalian Respiratory Tract.
Bertram, Stephanie; Thiele, Swantje; Dreier, Carola; Resa-Infante, Patricia; Preuß, Annette; van Riel, Debby; Mok, Chris K P; Schwalm, Folker; Peiris, Joseph S M; Klenk, Hans-Dieter; Gabriel, Gülsah.
Afiliação
  • Bertram S; Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany; Center for Structural and Cellular Biology in Medicine, University of Lübeck, Lübeck, Germany.
  • Thiele S; Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
  • Dreier C; Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
  • Resa-Infante P; Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
  • Preuß A; Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
  • van Riel D; Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany; Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands.
  • Mok CKP; Centre of Influenza Research, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; The University of Hong Kong-Pasteur Research Pole, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
  • Schwalm F; Institute of Virology, Philipps University Marburg, Marburg, Germany.
  • Peiris JSM; Centre of Influenza Research, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; The University of Hong Kong-Pasteur Research Pole, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
  • Klenk HD; Institute of Virology, Philipps University Marburg, Marburg, Germany.
  • Gabriel G; Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany; Center for Structural and Cellular Biology in Medicine, University of Lübeck, Lübeck, Germany. Electronic address: guelsah.gabriel@hpi.uni-hamburg.de.
Am J Pathol ; 187(4): 831-840, 2017 Apr.
Article em En | MEDLINE | ID: mdl-28189564
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sistema Respiratório / Replicação Viral / Alfa Carioferinas / Subtipo H7N9 do Vírus da Influenza A / Mamíferos Limite: Animals / Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sistema Respiratório / Replicação Viral / Alfa Carioferinas / Subtipo H7N9 do Vírus da Influenza A / Mamíferos Limite: Animals / Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article