dc.contributor.author
Knepper, Jessica
dc.contributor.author
Schierhorn, Kristina L
dc.contributor.author
Becher, Anne
dc.contributor.author
Budt, Matthias
dc.contributor.author
Tönnies, Mario
dc.contributor.author
Bauer, Torsten T.
dc.contributor.author
Schneider, Paul
dc.contributor.author
Neudecker, Jens
dc.contributor.author
Rückert, Jens C.
dc.contributor.author
Gruber, Achim Dieter
dc.contributor.author
Suttorp, Norbert
dc.contributor.author
Schweiger, Brunhilde
dc.contributor.author
Hippenstiel, Stefan
dc.contributor.author
Hocke, Andreas C.
dc.contributor.author
Wolff, Thorsten
dc.date.accessioned
2018-06-08T03:53:14Z
dc.date.available
2015-06-18T06:53:07.851Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/16144
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-20328
dc.description.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. 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.
en
dc.rights.uri
http://creativecommons.org/licenses/by-nc-sa/3.0/
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::630 Landwirtschaft
dc.title
The novel human influenza A(H7N9) virus is naturally adapted to efficient
growth in human lung tissue
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation
mBio. - 4 (2013), 5, Artikel Nr. e00601-13
dc.identifier.sepid
32267
dcterms.bibliographicCitation.doi
10.1128/mBio.00601-13
dcterms.bibliographicCitation.url
http://dx.doi.org/10.1128/mBio.00601-13
refubium.affiliation
Veterinärmedizin
de
refubium.affiliation.other
Institut für Tierpathologie
refubium.mycore.fudocsId
FUDOCS_document_000000022522
refubium.note.author
Der Artikel wurde in einer Open-Access-Zeitschrift publiziert.
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000005088
dcterms.accessRights.openaire
open access
dcterms.isPartOf.issn
2150-7511