Avian Influenza Virus: Deciphering receptor interactions and their role in interspecies transmission

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Avian Influenza Virus : Deciphering receptor interactions and their role in interspecies transmission

Eriksson, Per (författare): Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Zoonosis Science Center

Ellström, Patrik, docent (preses): Uppsala universitet,Institutionen för medicinska vetenskaper

Olsen, Björn, professor (preses): Uppsala universitet,Institutionen för medicinska vetenskaper

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Järhult, Josef D., docent (preses): Uppsala universitet,Institutionen för medicinska vetenskaper

Lundkvist, Åke, professor (preses): Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi

Waldenström, Jonas, professor (preses): Linnaeus University

Klenk, Hans-Dieter, Professor Dr. (opponent): Philipps Universität, Marburg

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ISBN 9789151307978
Uppsala : Acta Universitatis Upsaliensis, 2019
Engelska 72 s.
Serie: Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, 1651-6206 ; 1609

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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)

Abstract Ämnesord

Stäng

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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

Nyckelord

birds
glycobiology
glycovirology
host range
mixing vessel
virus attachment
Medical Virology
Medicinsk virologi

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vet (ämneskategori)
dok (ämneskategori)

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