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Nature 567, 109-112 (2019)
Zoonotic influenza A viruses of avian origin can cause severe disease in individuals, or even global pandemics, and thus pose a threat to human populations. Waterfowl and shorebirds are believed to be the reservoir for all influenza A viruses, but this has recently been challenged by the identification of novel influenza A viruses in bats(1,2). The major bat influenza A virus envelope glycoprotein, haemagglutinin, does not bind the canonical influenza A virus receptor, sialic acid or any other glycan(1,3,4), despite its high sequence and structural homology with conventional haemagglutinins. This functionally uncharacterized plasticity of the bat influenza A virus haemagglutinin means the tropism and zoonotic potential of these viruses has not been fully determined. Here we show, using transcriptomic profiling of susceptible versus non-susceptible cells in combination with genome-wide CRISPR-Cas9 screening, that the major histocompatibility complex class II (MHC-II) human leukocyte antigen DR isotype (HLA-DR) is an essential entry determinant for bat influenza A viruses. Genetic ablation of the HLA-DR alpha a-chain rendered cells resistant to infection by bat influenza A virus, whereas ectopic expression of the HLA-DR complex in non-susceptible cells conferred susceptibility. Expression of MHC-II from different bat species, pigs, mice or chickens also conferred susceptibility to infection. Notably, the infection of mice with bat influenza A virus resulted in robust virus replication in the upper respiratory tract, whereas mice deficient for MHC-II were resistant. Collectively, our data identify MHC-II as a crucial entry mediator for bat influenza A viruses in multiple species, which permits a broad vertebrate tropism.
Impact Factor
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Times Cited
Times Cited
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Anmerkungen
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Receptor-binding; A Virus; Expression; H17n10
Sprache
Veröffentlichungsjahr
2019
HGF-Berichtsjahr
2019
ISSN (print) / ISBN
0028-0836
e-ISSN
1476-4687
Zeitschrift
Nature
Quellenangaben
Band: 567,
Heft: 7746,
Seiten: 109-112
Verlag
Nature Publishing Group
Verlagsort
London
Begutachtungsstatus
Peer reviewed
Institut(e)
Helmholtz Pioneer Campus (HPC)
POF Topic(s)
30201 - Metabolic Health
Forschungsfeld(er)
Pioneer Campus
PSP-Element(e)
G-510002-001
WOS ID
WOS:000460426900051
Scopus ID
85062613906
PubMed ID
30787439
Erfassungsdatum
2019-03-15