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Karakus, U.* ; Thamamongood, T.* ; Ciminski, K.* ; Ran, W.* ; Günther, S.C.* ; Pohl, M.O.* ; Eletto, D.* ; Jeney, C.* ; Hoffmann, D.* ; Reiche, S.* ; Schinköthe, J.* ; Ulrich, R.* ; Wiener, J. ; Hayes, M.G.B.* ; Chang, M.W.* ; Hunziker, A.* ; Yángüez, E.* ; Aydillo, T.* ; Krammer, F.* ; Oderbolz, J.* ; Meier, M. ; Oxenius, A.* ; Halenius, A.* ; Zimmer, G.* ; Benner, C.* ; Hale, B.G.* ; García-Sastre, A.* ; Beer, M.* ; Schwemmle, M.* ; Stertz, S.*

MHC class II proteins mediate cross-species entry of bat influenza viruses.

Nature 567, 109-112 (2019)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Receptor-binding; A Virus; Expression; H17n10
ISSN (print) / ISBN 0028-0836
e-ISSN 1476-4687
Journal Nature
Quellenangaben Volume: 567, Issue: 7746, Pages: 109-112 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Helmholtz Pioneer Campus (HPC)