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Evolution of high pathogenicity of H5 avian influenza virus: haemagglutinin cleavage site selection of reverse-genetics mutants during passage in chickens

Luczo, Jasmina M., Tachedjian, Mary, Harper, Jennifer A., Payne, Jean S., Butler, Jeffrey M., Sapats, Sandra I., Lowther, Suzanne L., Michalski, Wojtek P., Stambas, John and Bingham, John 2018, Evolution of high pathogenicity of H5 avian influenza virus: haemagglutinin cleavage site selection of reverse-genetics mutants during passage in chickens, Scientific reports, vol. 8, no. 1, pp. 1-13, doi: 10.1038/s41598-018-29944-z.

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Title Evolution of high pathogenicity of H5 avian influenza virus: haemagglutinin cleavage site selection of reverse-genetics mutants during passage in chickens
Author(s) Luczo, Jasmina M.
Tachedjian, Mary
Harper, Jennifer A.
Payne, Jean S.
Butler, Jeffrey M.
Sapats, Sandra I.
Lowther, Suzanne L.
Michalski, Wojtek P.
Stambas, JohnORCID iD for Stambas, John orcid.org/0000-0002-5690-2551
Bingham, John
Journal name Scientific reports
Volume number 8
Issue number 1
Article ID 11518
Start page 1
End page 13
Total pages 13
Publisher Nature Publishing Group
Place of publication London, Eng.
Publication date 2018-08-01
ISSN 2045-2322
Keyword(s) Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
A VIRUSES
SWISS-MODEL
HONG-KONG
AMINO-ACIDS
FURIN
ACTIVATION
VIRULENCE
CELLS
ENDOPROTEASE
PATHOBIOLOGY
Summary Low pathogenicity avian influenza viruses (LPAIVs) are generally asymptomatic in their natural avian hosts. LPAIVs can evolve into highly pathogenic forms, which can affect avian and human populations with devastating consequences. The switch to highly pathogenic avian influenza virus (HPAIV) from LPAIV precursors requires the acquisition of multiple basic amino acids in the haemagglutinin cleavage site (HACS) motif. Through reverse genetics of an H5N1 HPAIV, and experimental infection of chickens, we determined that viruses containing five or more basic amino acids in the HACS motif were preferentially selected over those with three to four basic amino acids, leading to rapid replacement with virus types containing extended HACS motifs. Conversely, viruses harbouring low pathogenicity motifs containing two basic amino acids did not readily evolve to extended forms, suggesting that a single insertion of a basic amino acid into the cleavage site motif of low-pathogenic viruses may lead to escalating selection for extended motifs. Our results may explain why mid-length forms are rarely detected in nature. The stability of the short motif suggests that pathogenicity switching may require specific conditions of intense selection pressure (such as with high host density) to boost selection of the initial mid-length HACS forms.
Language eng
DOI 10.1038/s41598-018-29944-z
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2018, The Authors
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30112233

Document type: Journal Article
Collections: School of Medicine
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.