CMAS and ST3GAL4 Play an Important Role in the Adsorption of Influenza Virus by Affecting the Synthesis of Sialic Acid Receptors.

CMAS and ST3GAL4 Play an Important Role in the Adsorption of Influenza Virus by Affecting the Synthesis of Sialic Acid Receptors.
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CMAS和ST3GAL4通过影响唾液酸受体的合成在流感病毒的吸附中发挥重要作用

DOI:
10.3390/ijms22116081
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发表时间:
2021-06-04
影响因子:
5.6
通讯作者:
Zhou H
Zhou H
中科院分区:
生物学2区
文献类型:
--
作者:
Zhao Y;Zou J;Gao Q;Xie S;Cao J;Zhou H

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甲型流感病毒(IAV)通过将病毒包膜上的血凝素(HA)附着到细胞表面上的唾液酸(SA)受体来启动感染。重要的是,人IAV的HA对α-2,6-连接的SA受体具有更高的亲和力,并且禽株偏好α-2,3-连接的SA受体,而猪株对两种SA受体都具有强亲和力。CMAS和ST 3GAL 4基因是IAV附着和进入宿主所必需的。CMAS和ST 3GAL 4的缺失阻碍了唾液酸受体的合成,这反过来又阻止了IAV的吸附。此外,CMAS的敲除对猪、禽和人IAV的吸附有影响。ST 3GAL 4基因敲除对猪和禽IAV的吸附有抑制作用,对禽IAV的影响更为明显,而对人IAV的吸附无影响。总的来说,我们的研究结果表明,敲除CMAS和ST 3GAL 4通过抑制SA受体的合成来负调控IAV复制,这也为未来基因编辑动物的生产提供了新的见解。
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.
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