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  • Cellular glycan modification by B3GAT1 broadly restricts influenza virus infection.

Cellular glycan modification by B3GAT1 broadly restricts influenza virus infection.

Nature communications (2022-10-31)
Joseph D Trimarco, Sarah L Nelson, Ryan R Chaparian, Alexandra I Wells, Nathan B Murray, Parastoo Azadi, Carolyn B Coyne, Nicholas S Heaton
摘要

Communicable respiratory viral infections pose both epidemic and pandemic threats and broad-spectrum antiviral strategies could improve preparedness for these events. To discover host antiviral restriction factors that may act as suitable targets for the development of host-directed antiviral therapies, we here conduct a whole-genome CRISPR activation screen with influenza B virus (IBV). A top hit from our screen, beta-1,3-glucuronyltransferase 1 (B3GAT1), effectively blocks IBV infection. Subsequent studies reveal that B3GAT1 activity prevents cell surface sialic acid expression. Due to this mechanism of action, B3GAT1 expression broadly restricts infection with viruses that require sialic acid for entry, including Victoria and Yamagata lineage IBVs, H1N1/H3N2 influenza A viruses (IAVs), and the unrelated enterovirus D68. To understand the potential utility of B3GAT1 induction as an antiviral strategy in vivo, we specifically express B3GAT1 in the murine respiratory epithelium and find that overexpression is not only well-tolerated, but also protects female mice from a lethal viral challenge with multiple influenza viruses, including a pandemic-like H1N1 IAV. Thus, B3GAT1 may represent a host-directed broad-spectrum antiviral target with utility against clinically relevant respiratory viruses.

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Sigma-Aldrich
抗HNK-1/N-CAM (CD57) 小鼠单克隆抗体 小鼠抗, clone VC1.1, purified from hybridoma cell culture
Sigma-Aldrich
Monoclonal Anti-B3GAT1 antibody produced in mouse, Prestige Antibodies® Powered by Atlas Antibodies, clone CL9499, purified immunoglobulin, buffered aqueous glycerol solution
Sigma-Aldrich
Anti-B3GAT1 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody