Evolutionarily conserved amino acids in MHC-II mediate bat influenza A virus entry into human cells

Abstract: The viral hemagglutinins of conventional influenza A viruses (IAVs) bind to sialylated glycans on host cell surfaces for attachment and subsequent infection. In contrast, hemagglutinins of bat-derived IAVs target major histocompatibility complex class II (MHC-II) for cell entry. MHC-II proteins from various vertebrate species can facilitate infection with the bat IAV H18N11. Yet, it has been difficult to biochemically determine the H18:MHC-II binding. Here, we followed a different approach and generated MHC-II chimeras from the human leukocyte antigen DR (HLA-DR), which supports H18-mediated entry, and the nonclassical MHC-II molecule HLA-DM, which does not. In this context, viral entry was supported only by a chimera containing the HLA-DR α1, α2, and β1 domains. Subsequent modeling of the H18:HLA-DR interaction identified the α2 domain as central for this interaction. Further mutational analyses revealed highly conserved amino acids within loop 4 (N149) and β-sheet 6 (V190) of the α2 domain as critical for virus entry. This suggests that conserved residues in the α1, α2, and β1 domains of MHC-II mediate H18-binding and virus propagation. The conservation of MHC-II amino acids, which are critical for H18N11 binding, may explain the broad species specificity of this virus

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• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: PLOS biology. - 21, 7 (2023) , e3002182, ISSN: 1545-7885

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2023
• Creator: Olajide, Okikiola M. ; Osman, Maria Kaukab ; Robert, Jonathan ; Kessler, Susanne ; Toews, Lina Kathrin ; Thamamongood, Thiprampai ; Neefjes, Jacques ; Wrobel, Antoni G. ; Schwemmle, Martin ; Ciminski, Kevin ; Reuther, Peter

Further information

• DOI: 10.1371/journal.pbio.3002182
• URN: urn:nbn:de:bsz:25-freidok-2379054
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.