Citation: Lei Yu, Xinjin Liu, Xiaoqin Wei, Junrui Ren, Xueyun Wang, Shuwen Wu, Ke Lan. C1QTNF5 is a novel attachment factor that facilitates the entry of influenza A virus .VIROLOGICA SINICA, 2024, 39(2) : 277-289.  http://dx.doi.org/10.1016/j.virs.2024.01.003

C1QTNF5 is a novel attachment factor that facilitates the entry of influenza A virus

  • Corresponding author: Shuwen Wu, shuwenwu@whu.edu.cn
    Ke Lan, klan@whu.edu.cn
  • Received Date: 17 October 2023
    Accepted Date: 16 January 2024
    Available online: 20 January 2024
  • Influenza A virus (IAV) binds sialic acid receptors on the cell surface to enter the host cells, which is the key step in initiating infection, transmission and pathogenesis. Understanding the factors that contribute to the highly efficient entry of IAV into human cells will help elucidate the mechanism of viral entry and pathogenicity, and provide new targets for intervention. In the present study, we reported a novel membrane protein, C1QTNF5, which binds to the hemagglutinin protein of IAV and promotes IAV infection in vitro and in vivo. We found that the HA1 region of IAV hemagglutinin is critical for the interaction with C1QTNF5 protein, and C1QTNF5 interacts with hemagglutinin mainly through its N-terminus (1–103 aa). In addition, we further demonstrated that overexpression of C1QTNF5 promotes IAV entry, while blocking the interaction between C1QTNF5 and IAV hemagglutinin greatly inhibits viral entry. However, C1QTNF5 does not function as a receptor to mediate IAV infection in sialic acid-deficient CHO-Lec2 cells, but promotes IAV to attach to these cells, suggesting that C1QTNF5 is an important attachment factor for IAV. This work reveals C1QTNF5 as a novel IAV attachment factor and provides a new perspective for antiviral strategies.

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    C1QTNF5 is a novel attachment factor that facilitates the entry of influenza A virus

      Corresponding author: Shuwen Wu, shuwenwu@whu.edu.cn
      Corresponding author: Ke Lan, klan@whu.edu.cn
    • a. State Key Laboratory of Virology, Medical Research Institute, College of Life Sciences, Wuhan University, Wuhan, 430072, China;
    • b. Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, 430072, China;
    • c. Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430072, China

    Abstract: Influenza A virus (IAV) binds sialic acid receptors on the cell surface to enter the host cells, which is the key step in initiating infection, transmission and pathogenesis. Understanding the factors that contribute to the highly efficient entry of IAV into human cells will help elucidate the mechanism of viral entry and pathogenicity, and provide new targets for intervention. In the present study, we reported a novel membrane protein, C1QTNF5, which binds to the hemagglutinin protein of IAV and promotes IAV infection in vitro and in vivo. We found that the HA1 region of IAV hemagglutinin is critical for the interaction with C1QTNF5 protein, and C1QTNF5 interacts with hemagglutinin mainly through its N-terminus (1–103 aa). In addition, we further demonstrated that overexpression of C1QTNF5 promotes IAV entry, while blocking the interaction between C1QTNF5 and IAV hemagglutinin greatly inhibits viral entry. However, C1QTNF5 does not function as a receptor to mediate IAV infection in sialic acid-deficient CHO-Lec2 cells, but promotes IAV to attach to these cells, suggesting that C1QTNF5 is an important attachment factor for IAV. This work reveals C1QTNF5 as a novel IAV attachment factor and provides a new perspective for antiviral strategies.

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