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

Lei Yu; Xinjin Liu; Xiaoqin Wei; Junrui Ren; Xueyun Wang; Shuwen Wu; Ke Lan

doi:10.1016/j.virs.2024.01.003

April 2024

. doi: 10.1016/j.virs.2024.01.003

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是一种新型吸附因子促进甲型流感病毒进入

余雷 ^a ,
刘欣瑾 ^a ,
魏小琴 ^a ,
任军瑞 ^a ,
王雪云 ^a ,
吴叔文 ^a,, ,
蓝柯 ^a,b,c,,

a. 武汉大学病毒学国家重点实验室, 医学研究院, 生命科学学院;
b. 武汉大学免疫与代谢前沿科学中心;
c. 武汉大学泰康生命医学中心

通讯作者： 吴叔文, shuwenwu@whu.edu.cn; 蓝柯, klan@whu.edu.cn
收稿日期： 2023-10-17
录用日期： 2024-01-16

摘要

甲型流感病毒(Influenza A virus, IAV)通过结合细胞表面唾液酸（Sialic acid，SA）受体进入宿主细胞，这是启动感染、传播和致病的关键步骤。了解导致IAV高效进入人类细胞的因素将有助于阐明病毒进入和致病的机制，并提供新的干预靶点。在本研究中，我们报道了一种新的膜蛋白C1QTNF5，它与IAV的血凝素（Hemagglutinin，HA）蛋白结合并在体内外促进IAV感染。鉴定出IAV血凝素的HA1区域是与C1QTNF5蛋白相互作用的关键区域，而C1QTNF5主要通过其N端(1- 103aa)与血凝素相互作用。此外，我们进一步发现过表达C1QTNF5可促进IAV进入，而阻断C1QTNF5和IAV血凝素之间的相互作用极大地抑制了病毒的进入。然而，在唾液酸缺陷的CHO-Lec2细胞中，C1QTNF5不能作为独立受体介导IAV感染，而是促进IAV附着在这些细胞上，这表明C1QTNF5是IAV的重要吸附因子。这项工作揭示了C1QTNF5作为一种新的IAV吸附因子，为抗病毒策略提供了新的视角。
- C1QTNF5
- , 甲型流感病毒
- , 病毒进入
- , 血凝素
- , 吸附因子

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

Lei Yu ^a ,
Xinjin Liu ^a ,
Xiaoqin Wei ^a ,
Junrui Ren ^a ,
Xueyun Wang ^a ,
Shuwen Wu ^a,, ,
Ke Lan ^a,b,c,,

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

Corresponding author: Shuwen Wu, shuwenwu@whu.edu.cn Ke Lan, klan@whu.edu.cn
Received Date: 17 October 2023
Accepted Date: 16 January 2024

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.
- C1QTNF5
- , Influenza A virus
- , Viral entry
- , Hemagglutinin
- , Attachment factor

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