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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Feb 04, 2022 |
| Title |
MHC class II proteins mediate cross-species entry of bat influenza viruses |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| Summary |
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. The major bat influenza A virus envelope glycoprotein, haemagglutinin, does not bind the canonical influenza A virus receptor, sialic acid or any other glycan, 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.
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| Overall design |
Positive selection CRISPR screen with VSV-H18 in U-87MG cells
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| Contributor(s) |
Karakus U, Stertz S |
| Citation(s) |
30787439 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| U19 AI135972 |
Fluomics: The Next Generation |
MOUNT SINAI SCHOOL OF MEDICINE |
Adolfo Garcia-Sastre |
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| Submission date |
Feb 04, 2022 |
| Last update date |
Feb 04, 2022 |
| Contact name |
Max Chang |
| E-mail(s) |
mchang@ucsd.edu
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| Organization name |
University of California, San Diego
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| Street address |
9500 Gilman Drive
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| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92093 |
| Country |
USA |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA803440 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE196122_gene_summary.txt.gz |
485.9 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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