Tweet
mBio. The Novel Human Influenza A(H7N9) Virus Is Naturally Adapted to Efficient Growth in Human Lung Tissue
[Source: mBio, full page: (LINK). Abstract, edited.]
The Novel Human Influenza A(H7N9) Virus Is Naturally Adapted to Efficient Growth in Human Lung Tissue
Jessica Knepper<SUP>a</SUP>, Kristina L. Schierhorn<SUP>a</SUP>, Anne Becher<SUP>b</SUP>, Matthias Budt<SUP>a</SUP>, Mario T?nnies<SUP>c</SUP>, Torsten T. Bauer<SUP>c</SUP>, Paul Schneider<SUP>d</SUP>, Jens Neudecker<SUP>e</SUP>, Jens C. R?ckert<SUP>e</SUP>, Achim D. Gruber<SUP>f</SUP>, Norbert Suttorp<SUP>b</SUP>, Brunhilde Schweiger<SUP>a</SUP>, Stefan Hippenstiel<SUP>b</SUP>, Andreas C. Hocke<SUP>b</SUP>, Thorsten Wolff<SUP>a</SUP>
<SUP></SUP>
Author Affiliations: Division of Influenza and Other Respiratory Viruses, Robert Koch-Institut, Berlin, Germany<SUP>a </SUP>Department of Internal Medicine/Infectious Diseases and Respiratory Medicine, Charit?, Universit?tsmedizin Berlin, Berlin, Germany<SUP>b </SUP>HELIOS Clinic Emil von Behring, Department of Pneumology and Department of Thoracic Surgery, Chest Hospital Heckeshorn, Berlin, Germany<SUP>c </SUP>Department for General and Thoracic Surgery, DRK Clinics, Berlin, Germany<SUP>d </SUP>Department of General, Visceral, Vascular and Thoracic Surgery, Universit?tsmedizin Berlin, Charit? Campus Mitte, Berlin, Germany<SUP>e </SUP>Department of Veterinary Pathology, College of Veterinary Medicine, Freie Universit?t Berlin, Berlin, Germany<SUP>f</SUP>
<SUP></SUP>
Address correspondence to Thorsten Wolff, WolffT@RKI.de.
J.K. and K.L.S. contributed equally to this work.
Editor Peter Palese, Icahn School of Medicine at Mount Sinai
ABSTRACT
A novel influenza A virus (IAV) of the H7N9 subtype has been isolated from severely diseased patients with pneumonia and acute respiratory distress syndrome and, apparently, from healthy poultry in March 2013 in Eastern China. We evaluated replication, tropism, and cytokine induction of the A/Anhui/1/2013 (H7N9) virus isolated from a fatal human infection and two low-pathogenic avian H7 subtype viruses in a human lung organ culture system mimicking infection of the lower respiratory tract. The A(H7N9) patient isolate replicated similarly well as a seasonal IAV in explanted human lung tissue, whereas avian H7 subtype viruses propagated poorly. Interestingly, the avian H7 strains provoked a strong antiviral type I interferon (IFN-I) response, whereas the A(H7N9) virus induced only low IFN levels. Nevertheless, all viruses analyzed were detected predominantly in type II pneumocytes, indicating that the A(H7N9) virus does not differ in its cellular tropism from other avian or human influenza viruses. Tissue culture-based studies suggested that the low induction of the IFN-β promoter correlated with an efficient suppression by the viral NS1 protein. These findings demonstrate that the zoonotic A(H7N9) virus is unusually well adapted to efficient propagation in human alveolar tissue, which most likely contributes to the severity of lower respiratory tract disease seen in many patients.
IMPORTANCE
Humans are usually not infected by avian influenza A viruses (IAV), but this large group of viruses contributes to the emergence of human pandemic strains. Transmission of virulent avian IAV to humans is therefore an alarming event that requires assessment of the biology as well as pathogenic and pandemic potentials of the viruses in clinically relevant models. Here, we demonstrate that an early virus isolate from the recent A(H7N9) outbreak in Eastern China replicated as efficiently as human-adapted IAV in explanted human lung tissue, whereas avian H7 subtype viruses were unable to propagate. Robust replication of the H7N9 strain correlated with a low induction of antiviral beta interferon (IFN-β), and cell-based studies indicated that this is due to efficient suppression of the IFN response by the viral NS1 protein. Thus, explanted human lung tissue appears to be a useful experimental model to explore the determinants facilitating cross-species transmission of the H7N9 virus to humans.
Footnotes
Citation Knepper J, Schierhorn KL, Becher A, Budt M, T?nnies M, Bauer TT, Schneider P, Neudecker J, R?ckert JC, Gruber AD, Suttorp N, Schweiger B, Hippenstiel S, Hocke AC, Wolff T. 2013. The novel human influenza A(H7N9) virus is naturally adapted to efficient growth in human lung tissue. mBio 4(5):e00601-13. doi:10.1128/mBio.00601-13.
Received 1 August 2013. Accepted 23 September 2013. Published 8 October 2013
Copyright ? 2013 Knepper et al.
This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
-
------
The Novel Human Influenza A(H7N9) Virus Is Naturally Adapted to Efficient Growth in Human Lung Tissue
Jessica Knepper<SUP>a</SUP>, Kristina L. Schierhorn<SUP>a</SUP>, Anne Becher<SUP>b</SUP>, Matthias Budt<SUP>a</SUP>, Mario T?nnies<SUP>c</SUP>, Torsten T. Bauer<SUP>c</SUP>, Paul Schneider<SUP>d</SUP>, Jens Neudecker<SUP>e</SUP>, Jens C. R?ckert<SUP>e</SUP>, Achim D. Gruber<SUP>f</SUP>, Norbert Suttorp<SUP>b</SUP>, Brunhilde Schweiger<SUP>a</SUP>, Stefan Hippenstiel<SUP>b</SUP>, Andreas C. Hocke<SUP>b</SUP>, Thorsten Wolff<SUP>a</SUP>
<SUP></SUP>
Author Affiliations: Division of Influenza and Other Respiratory Viruses, Robert Koch-Institut, Berlin, Germany<SUP>a </SUP>Department of Internal Medicine/Infectious Diseases and Respiratory Medicine, Charit?, Universit?tsmedizin Berlin, Berlin, Germany<SUP>b </SUP>HELIOS Clinic Emil von Behring, Department of Pneumology and Department of Thoracic Surgery, Chest Hospital Heckeshorn, Berlin, Germany<SUP>c </SUP>Department for General and Thoracic Surgery, DRK Clinics, Berlin, Germany<SUP>d </SUP>Department of General, Visceral, Vascular and Thoracic Surgery, Universit?tsmedizin Berlin, Charit? Campus Mitte, Berlin, Germany<SUP>e </SUP>Department of Veterinary Pathology, College of Veterinary Medicine, Freie Universit?t Berlin, Berlin, Germany<SUP>f</SUP>
<SUP></SUP>
Address correspondence to Thorsten Wolff, WolffT@RKI.de.
J.K. and K.L.S. contributed equally to this work.
Editor Peter Palese, Icahn School of Medicine at Mount Sinai
ABSTRACT
A novel influenza A virus (IAV) of the H7N9 subtype has been isolated from severely diseased patients with pneumonia and acute respiratory distress syndrome and, apparently, from healthy poultry in March 2013 in Eastern China. We evaluated replication, tropism, and cytokine induction of the A/Anhui/1/2013 (H7N9) virus isolated from a fatal human infection and two low-pathogenic avian H7 subtype viruses in a human lung organ culture system mimicking infection of the lower respiratory tract. The A(H7N9) patient isolate replicated similarly well as a seasonal IAV in explanted human lung tissue, whereas avian H7 subtype viruses propagated poorly. Interestingly, the avian H7 strains provoked a strong antiviral type I interferon (IFN-I) response, whereas the A(H7N9) virus induced only low IFN levels. Nevertheless, all viruses analyzed were detected predominantly in type II pneumocytes, indicating that the A(H7N9) virus does not differ in its cellular tropism from other avian or human influenza viruses. Tissue culture-based studies suggested that the low induction of the IFN-β promoter correlated with an efficient suppression by the viral NS1 protein. These findings demonstrate that the zoonotic A(H7N9) virus is unusually well adapted to efficient propagation in human alveolar tissue, which most likely contributes to the severity of lower respiratory tract disease seen in many patients.
IMPORTANCE
Humans are usually not infected by avian influenza A viruses (IAV), but this large group of viruses contributes to the emergence of human pandemic strains. Transmission of virulent avian IAV to humans is therefore an alarming event that requires assessment of the biology as well as pathogenic and pandemic potentials of the viruses in clinically relevant models. Here, we demonstrate that an early virus isolate from the recent A(H7N9) outbreak in Eastern China replicated as efficiently as human-adapted IAV in explanted human lung tissue, whereas avian H7 subtype viruses were unable to propagate. Robust replication of the H7N9 strain correlated with a low induction of antiviral beta interferon (IFN-β), and cell-based studies indicated that this is due to efficient suppression of the IFN response by the viral NS1 protein. Thus, explanted human lung tissue appears to be a useful experimental model to explore the determinants facilitating cross-species transmission of the H7N9 virus to humans.
Footnotes
Citation Knepper J, Schierhorn KL, Becher A, Budt M, T?nnies M, Bauer TT, Schneider P, Neudecker J, R?ckert JC, Gruber AD, Suttorp N, Schweiger B, Hippenstiel S, Hocke AC, Wolff T. 2013. The novel human influenza A(H7N9) virus is naturally adapted to efficient growth in human lung tissue. mBio 4(5):e00601-13. doi:10.1128/mBio.00601-13.
Received 1 August 2013. Accepted 23 September 2013. Published 8 October 2013
Copyright ? 2013 Knepper et al.
This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
-
------
Comment