tetano
Editor, Senior Moderator
J Infect Dis. (2012) doi: 10.1093/infdis/jis455 First published online: July 24, 2012
Influenza A viruses target type II pneumocytes in the human lung
Viola K. Weinheimer1,#,
Anne Becher2,#,
Mario T?nnies3,
Gudrun Holland4,
Jessica Knepper1,
Torsten T. Bauer3,
Paul Schneider5,
Jens Neudecker6,
Jens C. R?ckert6,
Kolja Szymanski2,
Bettina Temmesfeld-Wollbrueck2,
Achim D. Gruber7,
Norbert Bannert4,
Norbert Suttorp2,
Stefan Hippenstiel2,
Thorsten Wolff1,* and
Andreas C. Hocke2
+ Author Affiliations
1Div. of Influenza/Respiratory Viruses, Robert Koch-Institut, Nordufer 20, 13353 Berlin, Germany
2Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charit? Universit?tsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
3HELIOS Clinic Emil von Behring, Department of Pneumology and Department of Thoracic Surgery, Chest Hospital Heckeshorn, Walterh?ferstr. 11, 14165 Berlin, Germany
4Centre for Biological Safety 4, Robert Koch-Institut, Nordufer 20, 13353 Berlin, Germany
5Department for General and Thoracic Surgery, DRK Clinics, Drontheimer Strasse 39-40, 13359 Berlin, Germany
6Department of General, Visceral, Vascular and Thoracic Surgery, Universit?tsmedizin Berlin, Charit? Campus Mitte, 10117 Berlin, Germany
7Department of Veterinary Pathology, College of Veterinary Medicine, Freie Universit?t Berlin, Robert-von-Ostertag-Str. 15, 14163 Berlin, Germany
↵*corresponding author: Thorsten Wolff, Div. of Influenza/Respiratory Viruses, Robert Koch-Institut, Nordufer 20, 13353 Berlin, Germany, Phone: +49-30 18754-2278; Fax: +49-30-18754 2328; Email: wolfft@rki.de
↵# V.W. and A.B. contributed equally to this study
Abstract
Background. Highly pathogenic avian H5N1 influenza viruses preferentially infect alveolar type II pneumocytes in human lung. However, it is unknown whether this cellular tropism contributes to high viral virulence as the primary target cells of other influenza viruses have not been systematically studied.
Methods. We provide the first comparison of the replication, tropism and cytokine induction of human, highly pathogenic avian H5N1 and other animal influenza A viruses in primary human lung organ cultures.
Results. H5N1 and human-adapted H1N1 and H3N2 viruses replicated efficiently in the lung tissue, whereas classical swine and low pathogenic avian viruses propagated only poorly. Nevertheless, all viruses examined were detected almost exclusively in type II pneumocytes with a minor involvement of alveolar macrophages. Infection with low- and highly pathogenic avian viruses provoked a pronounced cyto- and chemokine induction while human and pandemic H1N1-2009 viruses triggered only weak responses.
Conclusions. These findings show that differences in the pathogenic potential of influenza A viruses in the human lung cannot be attributed to a distinct cellular tropism. Rather, high or low viral pathogenicity is associated with a strain-specific capacity to productively replicate in type II pneumocytes and to cope with the induced cytokine response.
http://jid.oxfordjournals.org/content/early/2012/07/24/infdis.jis455.abstract
Influenza A viruses target type II pneumocytes in the human lung
Viola K. Weinheimer1,#,
Anne Becher2,#,
Mario T?nnies3,
Gudrun Holland4,
Jessica Knepper1,
Torsten T. Bauer3,
Paul Schneider5,
Jens Neudecker6,
Jens C. R?ckert6,
Kolja Szymanski2,
Bettina Temmesfeld-Wollbrueck2,
Achim D. Gruber7,
Norbert Bannert4,
Norbert Suttorp2,
Stefan Hippenstiel2,
Thorsten Wolff1,* and
Andreas C. Hocke2
+ Author Affiliations
1Div. of Influenza/Respiratory Viruses, Robert Koch-Institut, Nordufer 20, 13353 Berlin, Germany
2Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charit? Universit?tsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
3HELIOS Clinic Emil von Behring, Department of Pneumology and Department of Thoracic Surgery, Chest Hospital Heckeshorn, Walterh?ferstr. 11, 14165 Berlin, Germany
4Centre for Biological Safety 4, Robert Koch-Institut, Nordufer 20, 13353 Berlin, Germany
5Department for General and Thoracic Surgery, DRK Clinics, Drontheimer Strasse 39-40, 13359 Berlin, Germany
6Department of General, Visceral, Vascular and Thoracic Surgery, Universit?tsmedizin Berlin, Charit? Campus Mitte, 10117 Berlin, Germany
7Department of Veterinary Pathology, College of Veterinary Medicine, Freie Universit?t Berlin, Robert-von-Ostertag-Str. 15, 14163 Berlin, Germany
↵*corresponding author: Thorsten Wolff, Div. of Influenza/Respiratory Viruses, Robert Koch-Institut, Nordufer 20, 13353 Berlin, Germany, Phone: +49-30 18754-2278; Fax: +49-30-18754 2328; Email: wolfft@rki.de
↵# V.W. and A.B. contributed equally to this study
Abstract
Background. Highly pathogenic avian H5N1 influenza viruses preferentially infect alveolar type II pneumocytes in human lung. However, it is unknown whether this cellular tropism contributes to high viral virulence as the primary target cells of other influenza viruses have not been systematically studied.
Methods. We provide the first comparison of the replication, tropism and cytokine induction of human, highly pathogenic avian H5N1 and other animal influenza A viruses in primary human lung organ cultures.
Results. H5N1 and human-adapted H1N1 and H3N2 viruses replicated efficiently in the lung tissue, whereas classical swine and low pathogenic avian viruses propagated only poorly. Nevertheless, all viruses examined were detected almost exclusively in type II pneumocytes with a minor involvement of alveolar macrophages. Infection with low- and highly pathogenic avian viruses provoked a pronounced cyto- and chemokine induction while human and pandemic H1N1-2009 viruses triggered only weak responses.
Conclusions. These findings show that differences in the pathogenic potential of influenza A viruses in the human lung cannot be attributed to a distinct cellular tropism. Rather, high or low viral pathogenicity is associated with a strain-specific capacity to productively replicate in type II pneumocytes and to cope with the induced cytokine response.
http://jid.oxfordjournals.org/content/early/2012/07/24/infdis.jis455.abstract