Abstract
Influenza A viruses (IAVs) initiate infection by attaching Hemagglutinin (HA) on the viral envelope to sialic acid (SA) receptors on the cell surface. Importantly, HA of human IAVs has a higher affinity for α-2,6-linked SA receptors, and avian strains prefer α-2,3-linked SA receptors, whereas swine strains have a strong affinity for both SA receptors. Host gene CMAS and ST3GAL4 were found to be essential for IAV attachment and entry. Loss of CMAS and ST3GAL4 hindered the synthesis of sialic acid receptors, which in turn prevented the adsorption of IAV. Further, the knockout of CMAS had an effect on the adsorption of swine, avian and human IAVs. However, ST3GAL4 knockout prevented the adsorption of swine and avian IAV and the impact on avian IAV was more distinct, whereas it had no effect on the adsorption of human IAV. Collectively, our findings demonstrate that knocking out CMAS and ST3GAL4 negatively regulated IAV replication by inhibiting the synthesis of SA receptors, which also provides new insights into the production of gene-edited animals in the future.
Highlights
Influenza A virus (IAV) is an upper respiratory pathogen in humans and animals, and it evolves rapidly and can lead to seasonal epidemics and occasional pandemics [1,2]
This study focuses on the host gene Cytidine monophosphate N-acetylneuraminic acid synthetase (CMAS) and ST3GAL4, which were included in the previous genome-wide CRISPR knockout screening
The virus titer was determined at 36 h post-infection, and the cell-survival rates under different multiplicities of infection (MOI) conditions were calculated at 72 hpi
Summary
Influenza A virus (IAV) is an upper respiratory pathogen in humans and animals, and it evolves rapidly and can lead to seasonal epidemics and occasional pandemics [1,2]. The biosynthesis of sialylated oligosaccharide sequences depends on the catalysis of the sialyltransferase family, and these enzymes transfer the sialic acid group in the active intermediate product, CMP-sialic acid, to the glycoprotein and terminal position on the sugar chain in different ways [8,11,12]. They are divided into different families (ST6Gal, ST6GalNAc, ST3Gal and ST8Sia) according to the types of glycosidic bonds newly formed after the transfer, and the ST3 family transfers sialic acid groups to galactose residues mainly based on α-2,3 glycosidic bond [11]
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