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Host range of influenza A virus H1 to H16 in dabbling vs. diving ducks based on tissue and receptor binding studies
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(English)Manuscript (preprint) (Other academic)
National Category
Microbiology
Identifiers
URN: urn:nbn:se:uu:diva-395405OAI: oai:DiVA.org:uu-395405DiVA, id: diva2:1362177
Available from: 2019-10-18 Created: 2019-10-18 Last updated: 2019-10-24
In thesis
1. Avian Influenza Virus: Deciphering receptor interactions and their role in interspecies transmission
Open this publication in new window or tab >>Avian Influenza Virus: Deciphering receptor interactions and their role in interspecies transmission
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Influenza A virus (IAV) annually infects approximately 5–15 % of the human population, causing ~500,000 deaths globally. Novel IAVs have emerged and spread pandemically in the human population, but have over time established endemic circulation with reduced pathogenicity causing seasonal influenza. The natural reservoir of IAVs is wild waterfowl. The past pandemics have been associated with host switch and have partly or entirely originated from birds, or adapted via passage through pigs (postulated IAV mixing vessel). Understanding IAV interspecies transmission mechanisms is essential for pandemic preparedness. Enzootic circulation of avian IAV (AIV) is concentrated to a few waterfowl species, while other bird species seldom are infected. A species barrier preventing IAV interspecies transmission has been suggested. To investigate IAV host range and mixing vessels, histochemistry studies were conducted with tissues from avian species, pigs, and humans. Virus adaptation to new hosts was studied by challenging tufted ducks and chickens with mallard-derived AIVs, together with AIV receptor tropism and glycoproteomic analysis of receptor distribution. Finally, receptor and tissue tropism in ducks was studied systematically for AIV (H1–16). More abundant AIV attachment to human than pig tissues was observed, questioning the pig mixing vessel theory. Attachment patterns of AIVs to bird tissues was generally broad with abundant attachment to trachea. However, among ducks, pronounced attachment was observed to colon of Anas spp., suggesting that intestinal infection might be restricted to Anas spp., whereas other species may be susceptible to respiratory infection. Tufted ducks and chickens could not be infected by intraesophageal inoculation further supporting this hypothesis. Glycan array analysis revealed 3’SLN, 3’STF, and their fucosylated and sulfated analogues as main AIV receptors. Moreover, AIV Neu5Acα2,6 recognition was widespread. Avian respiratory and intestinal tracts glycoproteomic analysis revealed that avian and mammalian receptor structures are much more similar than earlier thought. Furthermore, observed AIV subtype titer variation in challenged tufted ducks and chickens did not correlate with virus receptor tropism. In summary, this thesis suggests that IAV receptor recognition, in particular α2,3 vs. α2,6 sialylated receptor structures, is less important for the IAV interspecies barrier than previously thought.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2019. p. 72
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1609
Keywords
birds, glycobiology, glycovirology, host range, mixing vessel, virus attachment
National Category
Microbiology in the medical area
Research subject
Medical Virology
Identifiers
urn:nbn:se:uu:diva-395407 (URN)978-91-513-0797-8 (ISBN)
Public defence
2019-12-14, Trippelrummet, Navet, SciLifeLab, BMC, Husargatan 3, Uppsala, 09:15 (English)
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Supervisors
Available from: 2019-11-21 Created: 2019-10-24 Last updated: 2019-11-21

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