tetano
Editor, Senior Moderator
Nature. 2019 Feb 20. doi: 10.1038/s41586-019-0955-3. [Epub ahead of print]
[h=1]MHC class II proteins mediate cross-species entry of bat influenza viruses.[/h] Karakus U[SUP]1[/SUP], Thamamongood T[SUP]2,[/SUP][SUP]3,[/SUP][SUP]4,[/SUP][SUP]5[/SUP], Ciminski K[SUP]2,[/SUP][SUP]3[/SUP], Ran W[SUP]2,[/SUP][SUP]3[/SUP], G?nther SC[SUP]1[/SUP], Pohl MO[SUP]1[/SUP], Eletto D[SUP]1[/SUP], Jeney C[SUP]6[/SUP], Hoffmann D[SUP]7[/SUP], Reiche S[SUP]8[/SUP], Schink?the J[SUP]8[/SUP], Ulrich R[SUP]8[/SUP], Wiener J[SUP]9[/SUP], Hayes MGB[SUP]10[/SUP], Chang MW[SUP]10[/SUP], Hunziker A[SUP]1[/SUP], Y?ng?ez E[SUP]1[/SUP], Aydillo T[SUP]11,[/SUP][SUP]12[/SUP], Krammer F[SUP]11[/SUP], Oderbolz J[SUP]13[/SUP], Meier M[SUP]9[/SUP], Oxenius A[SUP]13[/SUP], Halenius A[SUP]2,[/SUP][SUP]3[/SUP], Zimmer G[SUP]14,[/SUP][SUP]15[/SUP], Benner C[SUP]10[/SUP], Hale BG[SUP]1[/SUP], Garc?a-Sastre A[SUP]11,[/SUP][SUP]12,[/SUP][SUP]16[/SUP], Beer M[SUP]7[/SUP], Schwemmle M[SUP]17,[/SUP][SUP]18[/SUP], Stertz S[SUP]19[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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[SUP]1,2[/SUP]. The major bat influenza A virus envelope glycoprotein, haemagglutinin, does not bind the canonical influenza A virus receptor, sialic acid or any other glycan[SUP]1,3,4[/SUP], 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 α-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.
PMID: 30787439 DOI: 10.1038/s41586-019-0955-3
[h=1]MHC class II proteins mediate cross-species entry of bat influenza viruses.[/h] Karakus U[SUP]1[/SUP], Thamamongood T[SUP]2,[/SUP][SUP]3,[/SUP][SUP]4,[/SUP][SUP]5[/SUP], Ciminski K[SUP]2,[/SUP][SUP]3[/SUP], Ran W[SUP]2,[/SUP][SUP]3[/SUP], G?nther SC[SUP]1[/SUP], Pohl MO[SUP]1[/SUP], Eletto D[SUP]1[/SUP], Jeney C[SUP]6[/SUP], Hoffmann D[SUP]7[/SUP], Reiche S[SUP]8[/SUP], Schink?the J[SUP]8[/SUP], Ulrich R[SUP]8[/SUP], Wiener J[SUP]9[/SUP], Hayes MGB[SUP]10[/SUP], Chang MW[SUP]10[/SUP], Hunziker A[SUP]1[/SUP], Y?ng?ez E[SUP]1[/SUP], Aydillo T[SUP]11,[/SUP][SUP]12[/SUP], Krammer F[SUP]11[/SUP], Oderbolz J[SUP]13[/SUP], Meier M[SUP]9[/SUP], Oxenius A[SUP]13[/SUP], Halenius A[SUP]2,[/SUP][SUP]3[/SUP], Zimmer G[SUP]14,[/SUP][SUP]15[/SUP], Benner C[SUP]10[/SUP], Hale BG[SUP]1[/SUP], Garc?a-Sastre A[SUP]11,[/SUP][SUP]12,[/SUP][SUP]16[/SUP], Beer M[SUP]7[/SUP], Schwemmle M[SUP]17,[/SUP][SUP]18[/SUP], Stertz S[SUP]19[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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[SUP]1,2[/SUP]. The major bat influenza A virus envelope glycoprotein, haemagglutinin, does not bind the canonical influenza A virus receptor, sialic acid or any other glycan[SUP]1,3,4[/SUP], 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 α-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.
PMID: 30787439 DOI: 10.1038/s41586-019-0955-3