Hemagglutinin of influenza A virus binds specifically to cell surface nucleolin and plays a role in virus internalization
Hemagglutinin of influenza A virus binds specifically to cell surface nucleolin and plays a role in virus internalization
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DOI：
10.1016/j.virol.2016.04.008
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发表时间：
2016-07-01
期刊：
影响因子：
3.7
通讯作者：
Yuen, Kwok-Yung
中科院分区：
文献类型：
--
作者：
Chan, Che-Man;Chu, Hin;Yuen, Kwok-Yung
甲型流感病毒的血凝素（HA）蛋白通过与靶细胞上的唾液酸结合来启动细胞进入。在当前的研究中，我们证明，除了唾液酸，流感A/波多黎各/8/34 H1N1（PR 8）病毒HA特异性结合细胞表面核仁素（NCL）。HA和NCL之间的相互作用最初用病毒覆盖蛋白结合试验（VOPBA）揭示，随后用免疫共沉淀法验证。重要的是，用NCL抗体抑制细胞表面NCL，用纯化的NCL蛋白阻断PR 8病毒，或用siRNA耗尽内源性NCL都显著降低了流感病毒内化。我们进一步证明，NCL是多种甲型流感病毒（包括H1N1、H3 N2、H5 N1和H7N9）进入所需的保守细胞因子。总体而言，我们的研究结果确定了NCL在流感病毒生命周期中的新作用，并确定了NCL作为甲型流感病毒进入宿主细胞表面蛋白之一。(C)2016 Elsevier Inc. All rights reserved.
The hemagglutinin (HA) protein of influenza A virus initiates cell entry by binding to sialic acids on target cells. In the current study, we demonstrated that in addition to sialic acids, influenza A/Puerto Rico/8/34 H1N1 (PR8) virus HA specifically binds to cell surface nucleolin (NCL). The interaction between HA and NCL was initially revealed with virus overlay protein binding assay (VOPBA) and subsequently verified with co-immunoprecipitation. Importantly, inhibiting cell surface NCL with NCL antibody, blocking PR8 viruses with purified NCL protein, or depleting endogenous NCL with siRNA all substantially reduced influenza virus internalization. We further demonstrated that NCL was a conserved cellular factor required for the entry of multiple influenza A viruses, including H1N1, H3N2, H5N1, and H7N9. Overall, our findings identified a novel role of NCL in influenza virus life cycle and established NCL as one of the host cell surface proteins for the entry of influenza A virus. (C) 2016 Elsevier Inc. All rights reserved.