TY  - JOUR
A1  - Schmier, Sonja
A1  - Mostafa, Ahmed
A1  - Haarmann, Thomas
A1  - Bannert, Norbert
A1  - Ziebuhr, John
A1  - Veljkovic, Veljko
A1  - Dietrich, Ursula
A1  - Pleschka, Stephan
T1  - In silico prediction and experimental confirmation of HA residues conferring enhanced human receptor specificity of H5N1 Influenza A viruses
T2  - Scientific reports
N2  - Newly emerging influenza A viruses (IAV) pose a major threat to human health by causing seasonal epidemics and/or pandemics, the latter often facilitated by the lack of pre-existing immunity in the general population. Early recognition of candidate pandemic influenza viruses (CPIV) is of crucial importance for restricting virus transmission and developing appropriate therapeutic and prophylactic strategies including effective vaccines. Often, the pandemic potential of newly emerging IAV is only fully recognized once the virus starts to spread efficiently causing serious disease in humans. Here, we used a novel phylogenetic algorithm based on the informational spectrum method (ISM) to identify potential CPIV by predicting mutations in the viral hemagglutinin (HA) gene that are likely to (differentially) affect critical interactions between the HA protein and target cells from bird and human origin, respectively. Predictions were subsequently validated by generating pseudotyped retrovirus particles and genetically engineered IAV containing these mutations and characterizing potential effects on virus entry and replication in cells expressing human and avian IAV receptors, respectively. Our data suggest that the ISM-based algorithm is suitable to identify CPIV among IAV strains that are circulating in animal hosts and thus may be a new tool for assessing pandemic risks associated with specific strains.
KW  - Computational models
KW  - Influenza virus
Y1  - 2015
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/50493
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-504934
SN  - 2045-2322
N1  - This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
VL  - 5
IS  - Art. 11434
SP  - 1
EP  - 16
PB  - Nature Publishing Group
CY  - London
ER  -