In Silico Prediction and Experimental Confirmation of HA Residues Conferring Enhanced Human Receptor Specificity of H5N1 Influenza A Viruses
Identifieur interne : 000606 ( Main/Exploration ); précédent : 000605; suivant : 000607In Silico Prediction and Experimental Confirmation of HA Residues Conferring Enhanced Human Receptor Specificity of H5N1 Influenza A Viruses
Auteurs : Sonja Schmier [Allemagne] ; Ahmed Mostafa [Allemagne, Égypte] ; Thomas Haarmann [Allemagne] ; Norbert Bannert [Allemagne] ; John Ziebuhr [Allemagne] ; Veljko Veljkovic [Serbie] ; Ursula Dietrich [Allemagne] ; Stephan Pleschka [Allemagne]Source :
- Scientific Reports [ 2045-2322 ] ; 2015.
Abstract
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.
Url:
DOI: 10.1038/srep11434
PubMed: 26091504
PubMed Central: 4473683
Affiliations:
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Frankfurt,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Mostafa, Ahmed" sort="Mostafa, Ahmed" uniqKey="Mostafa A" first="Ahmed" last="Mostafa">Ahmed Mostafa</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Institute of Medical Virology, Justus Liebig University Giessen</institution>, Schubertstrasse 81, Giessen,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Center of Scientific Excellence for Influenza Viruses, National Research Centre (NRC)</institution>, Dokki, Giza,<country>Egypt</country></nlm:aff><country xml:lang="fr">Égypte</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Haarmann, Thomas" sort="Haarmann, Thomas" uniqKey="Haarmann T" first="Thomas" last="Haarmann">Thomas Haarmann</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy</institution>, Paul-Ehrlich-Str. 42-44, Frankfurt,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bannert, Norbert" sort="Bannert, Norbert" uniqKey="Bannert N" first="Norbert" last="Bannert">Norbert Bannert</name><affiliation wicri:level="1"><nlm:aff id="a4"><institution>Robert-Koch-Institute, Division for HIV and other Retroviruses</institution>, Nordufer 20, Berlin,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Ziebuhr, John" sort="Ziebuhr, John" uniqKey="Ziebuhr J" first="John" last="Ziebuhr">John Ziebuhr</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Institute of Medical Virology, Justus Liebig University Giessen</institution>, Schubertstrasse 81, Giessen,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Veljkovic, Veljko" sort="Veljkovic, Veljko" uniqKey="Veljkovic V" first="Veljko" last="Veljkovic">Veljko Veljkovic</name><affiliation wicri:level="1"><nlm:aff id="a5"><institution>Centre for Multidisciplinary Research, Institute of Nuclear Sciences VINCA</institution>, Mihaila Petrovica 14, Belgrade,<country>Serbia</country></nlm:aff><country xml:lang="fr">Serbie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Dietrich, Ursula" sort="Dietrich, Ursula" uniqKey="Dietrich U" first="Ursula" last="Dietrich">Ursula Dietrich</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy</institution>, Paul-Ehrlich-Str. 42-44, Frankfurt,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Pleschka, Stephan" sort="Pleschka, Stephan" uniqKey="Pleschka S" first="Stephan" last="Pleschka">Stephan Pleschka</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Institute of Medical Virology, Justus Liebig University Giessen</institution>, Schubertstrasse 81, Giessen,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Scientific Reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>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.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Plotkin, J B" uniqKey="Plotkin J">J. B. Plotkin</name></author><author><name sortKey="Dushoff, J" uniqKey="Dushoff J">J. Dushoff</name></author><author><name sortKey="Levin, S A" uniqKey="Levin S">S. A. Levin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pereira, H G" uniqKey="Pereira H">H. G. Pereira</name></author><author><name sortKey="Rinaldi, A" uniqKey="Rinaldi A">A. Rinaldi</name></author><author><name sortKey="Nardelli, L" uniqKey="Nardelli L">L. Nardelli</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wright, P F" uniqKey="Wright P">P. F. 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Peng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alexander, D J" uniqKey="Alexander D">D. J. Alexander</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alexander, D J" uniqKey="Alexander D">D. J. Alexander</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, Z" uniqKey="Wang Z">Z. Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shi, W" uniqKey="Shi W">W. Shi</name></author><author><name sortKey="Shi, Y" uniqKey="Shi Y">Y. Shi</name></author><author><name sortKey="Wu, Y" uniqKey="Wu Y">Y. Wu</name></author><author><name sortKey="Liu, D" uniqKey="Liu D">D. Liu</name></author><author><name sortKey="Gao, G F" uniqKey="Gao G">G. F. Gao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, H" uniqKey="Chen H">H. Chen</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Allemagne</li><li>Serbie</li><li>Égypte</li></country></list><tree><country name="Allemagne"><noRegion><name sortKey="Schmier, Sonja" sort="Schmier, Sonja" uniqKey="Schmier S" first="Sonja" last="Schmier">Sonja Schmier</name></noRegion><name sortKey="Bannert, Norbert" sort="Bannert, Norbert" uniqKey="Bannert N" first="Norbert" last="Bannert">Norbert Bannert</name><name sortKey="Dietrich, Ursula" sort="Dietrich, Ursula" uniqKey="Dietrich U" first="Ursula" last="Dietrich">Ursula Dietrich</name><name sortKey="Haarmann, Thomas" sort="Haarmann, Thomas" uniqKey="Haarmann T" first="Thomas" last="Haarmann">Thomas Haarmann</name><name sortKey="Mostafa, Ahmed" sort="Mostafa, Ahmed" uniqKey="Mostafa A" first="Ahmed" last="Mostafa">Ahmed Mostafa</name><name sortKey="Pleschka, Stephan" sort="Pleschka, Stephan" uniqKey="Pleschka S" first="Stephan" last="Pleschka">Stephan Pleschka</name><name sortKey="Ziebuhr, John" sort="Ziebuhr, John" uniqKey="Ziebuhr J" first="John" last="Ziebuhr">John Ziebuhr</name></country><country name="Égypte"><noRegion><name sortKey="Mostafa, Ahmed" sort="Mostafa, Ahmed" uniqKey="Mostafa A" first="Ahmed" last="Mostafa">Ahmed Mostafa</name></noRegion></country><country name="Serbie"><noRegion><name sortKey="Veljkovic, Veljko" sort="Veljkovic, Veljko" uniqKey="Veljkovic V" first="Veljko" last="Veljkovic">Veljko Veljkovic</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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