Publication Date:
2015-09-30
Description:
Influenza A viruses pose a major public health threat by causing seasonal epidemics and sporadic pandemics. Their epidemiological success relies on airborne transmission from person to person; however, the viral properties governing airborne transmission of influenza A viruses are complex. Influenza A virus infection is mediated via binding of the viral haemagglutinin (HA) to terminally attached alpha2,3 or alpha2,6 sialic acids on cell surface glycoproteins. Human influenza A viruses preferentially bind alpha2,6-linked sialic acids whereas avian influenza A viruses bind alpha2,3-linked sialic acids on complex glycans on airway epithelial cells. Historically, influenza A viruses with preferential association with alpha2,3-linked sialic acids have not been transmitted efficiently by the airborne route in ferrets. Here we observe efficient airborne transmission of a 2009 pandemic H1N1 (H1N1pdm) virus (A/California/07/2009) engineered to preferentially bind alpha2,3-linked sialic acids. Airborne transmission was associated with rapid selection of virus with a change at a single HA site that conferred binding to long-chain alpha2,6-linked sialic acids, without loss of alpha2,3-linked sialic acid binding. The transmissible virus emerged in experimentally infected ferrets within 24 hours after infection and was remarkably enriched in the soft palate, where long-chain alpha2,6-linked sialic acids predominate on the nasopharyngeal surface. Notably, presence of long-chain alpha2,6-linked sialic acids is conserved in ferret, pig and human soft palate. Using a loss-of-function approach with this one virus, we demonstrate that the ferret soft palate, a tissue not normally sampled in animal models of influenza, rapidly selects for transmissible influenza A viruses with human receptor (alpha2,6-linked sialic acids) preference.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4592815/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4592815/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lakdawala, Seema S -- Jayaraman, Akila -- Halpin, Rebecca A -- Lamirande, Elaine W -- Shih, Angela R -- Stockwell, Timothy B -- Lin, Xudong -- Simenauer, Ari -- Hanson, Christopher T -- Vogel, Leatrice -- Paskel, Myeisha -- Minai, Mahnaz -- Moore, Ian -- Orandle, Marlene -- Das, Suman R -- Wentworth, David E -- Sasisekharan, Ram -- Subbarao, Kanta -- HHSN272200900007C/PHS HHS/ -- R01 GM057073/GM/NIGMS NIH HHS/ -- R37 GM057073-13/GM/NIGMS NIH HHS/ -- U19 AI110819/AI/NIAID NIH HHS/ -- U19-AI-110819/AI/NIAID NIH HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2015 Oct 1;526(7571):122-5. doi: 10.1038/nature15379. Epub 2015 Sep 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Department of Biological Engineering, Koch Institute for Integrative Cancer Research, Singapore-MIT Alliance for Research and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. ; J. Craig Venter Institute, Rockville, Maryland 20850, USA. ; Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26416728" target="_blank"〉PubMed〈/a〉
Keywords:
*Adaptation, Physiological/genetics
;
Animals
;
Epithelial Cells/metabolism/virology
;
Female
;
Ferrets/virology
;
Hemagglutinin Glycoproteins, Influenza Virus/genetics/metabolism
;
Humans
;
Influenza A Virus, H1N1 Subtype/chemistry/genetics/*physiology
;
Male
;
Molecular Sequence Data
;
Orthomyxoviridae Infections/transmission/virology
;
Palate, Soft/chemistry/*metabolism/*virology
;
Receptors, Virus/*metabolism
;
Respiratory System/cytology/metabolism/virology
;
*Selection, Genetic/genetics
;
Sialic Acids/chemistry/metabolism
;
Swine/virology
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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