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

Nature
Umut KarakusSilke Stertz

Abstract

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 bats1,2. The major bat influenza A virus envelope glycoprotein, haemagglutinin, does not bind the canonical influenza A virus receptor, sialic acid or any other glycan1,3,4, 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 α-chain rendered cells resistant to infection by bat influenza A virus, whereas ectopic expression of the HLA-DR complex in non-susc...Continue Reading

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Citations

Sep 19, 2019·Nature Microbiology·Kevin CiminskiMartin Schwemmle
Dec 25, 2019·Cold Spring Harbor Perspectives in Medicine·Michelle Wille, Edward C Holmes
Dec 25, 2019·Cold Spring Harbor Perspectives in Medicine·Nicholas C Wu, Ian A Wilson
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Oct 25, 2020·Trends in Molecular Medicine·Kevin CiminskiMartin Schwemmle
Dec 25, 2019·Cold Spring Harbor Perspectives in Medicine·Kevin Ciminski, Martin Schwemmle
Feb 13, 2021·Nature Communications·Yunkai ZhuRong Zhang
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Oct 27, 2021·Nature Communications·Guha Asthagiri ArunkumarFlorian Krammer

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Datasets Mentioned

BETA
CY125945.1

Methods Mentioned

BETA
proximity ligation assay
PCR
transfection
transgenic
FCS
flow cytometry
flow-assisted
genotyping
Illumina
Assay

Software Mentioned

STAR
FlowJo
R package edgeR
R package GenomicRanges from
Bioconductor
Python
MAGeCK
EdgeR
Ensembl
Actome

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