tetano
Editor, Senior Moderator
PLoS Biol
. 2023 Jul 6;21(7):e3002182.
doi: 10.1371/journal.pbio.3002182. eCollection 2023 Jul. Evolutionarily conserved amino acids in MHC-II mediate bat influenza A virus entry into human cells
Okikiola M Olajide[SUP] 1 2 3 4 [/SUP], Maria Kaukab Osman[SUP] 1 2 3 4 [/SUP], Jonathan Robert[SUP] 1 2 3 4 [/SUP], Susanne Kessler[SUP] 1 2 [/SUP], Lina Kathrin Toews[SUP] 1 2 [/SUP], Thiprampai Thamamongood[SUP] 5 [/SUP], Jacques Neefjes[SUP] 6 [/SUP], Antoni G Wrobel[SUP] 7 [/SUP], Martin Schwemmle[SUP] 1 2 [/SUP], Kevin Ciminski[SUP] 1 2 [/SUP], Peter Reuther[SUP] 1 2 [/SUP]
Affiliations
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.
. 2023 Jul 6;21(7):e3002182.
doi: 10.1371/journal.pbio.3002182. eCollection 2023 Jul. Evolutionarily conserved amino acids in MHC-II mediate bat influenza A virus entry into human cells
Okikiola M Olajide[SUP] 1 2 3 4 [/SUP], Maria Kaukab Osman[SUP] 1 2 3 4 [/SUP], Jonathan Robert[SUP] 1 2 3 4 [/SUP], Susanne Kessler[SUP] 1 2 [/SUP], Lina Kathrin Toews[SUP] 1 2 [/SUP], Thiprampai Thamamongood[SUP] 5 [/SUP], Jacques Neefjes[SUP] 6 [/SUP], Antoni G Wrobel[SUP] 7 [/SUP], Martin Schwemmle[SUP] 1 2 [/SUP], Kevin Ciminski[SUP] 1 2 [/SUP], Peter Reuther[SUP] 1 2 [/SUP]
Affiliations
- PMID: 37410798
- PMCID: PMC10325068
- DOI: 10.1371/journal.pbio.3002182
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.