<i>CMAS</i> and <i>ST3GAL4</i> Play an Important Role in the Adsorption of Influenza Virus by Affecting the Synthesis of Sialic Acid Receptors

• Main Authors: Yaxin Zhao, Jiahui Zou, Qingxia Gao, Shengsong Xie, Jiyue Cao, Hongbo Zhou
• Format: Article
• Language: English
• Published: MDPI AG 2021-06-01
• Series: International Journal of Molecular Sciences
• Subjects: <i>CMAS</i>; <i>ST3GAL4</i>; CRISPR/Cas9; influenza; sialic acid receptors
• Online Access: https://www.mdpi.com/1422-0067/22/11/6081

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 <i>CMAS</i> and <i>ST3GAL4</i> were found to be essential for IAV attachment and entry. Loss of <i>CMAS</i> and <i>ST3GAL4</i> hindered the synthesis of sialic acid receptors, which in turn prevented the adsorption of IAV. Further, the knockout of <i>CMAS</i> had an effect on the adsorption of swine, avian and human IAVs. However, <i>ST3GAL4</i> 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 <i>CMAS</i> and <i>ST3GAL4</i> 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.