蛋白激酶在流感病毒生命周期不同阶段的作用

Roles of kinases in the life cycle of influenza virus

摘要:

流感病毒持续危害全球公共卫生安全，引起人类和动物的传染性呼吸道疾病，每年导致全球数十万人死亡。流感病毒能够通过抗原转变和抗原漂移进化出新型毒株，从而对现有药物和疫苗产生耐药性。为了解决这个问题，亟须研究新的抗病毒靶点来开发新型抗病毒药物。流感病毒的基因产物通过多种宿主激酶的磷酸化而被广泛修饰。丝氨酸、苏氨酸或酪氨酸残基的可逆磷酸化动态调节病毒蛋白在其生命周期不同阶段的结构、功能和亚细胞定位。此外，蛋白激酶参与多个宿主信号传导过程，这些信号传导途径通过调节宿主细胞环境来影响病毒的复制，从而建立关键的病毒-宿主关系。这种对宿主激酶的依赖性为开发激酶抑制剂作为下一代宿主靶向疗法的抗流感病毒药物提供了理论基础。为了充分利用这一潜力，阐明流感病毒-宿主激酶相互作用网络至关重要。本综述的重点是概述宿主激酶参与调节流感病毒生命周期不同阶段(从吸附到组装出芽)的分子机制。通过评估不同宿主激酶及其在病毒生命周期中特定磷酸化的作用，对病毒-宿主激酶相互作用网络进行全面概述，这可能有助于揭示新型抗病毒药物的潜在作用靶点。

关键词:流感病毒;激酶;生命周期;感染

Abstract:

Influenza virus continues to pose a threat to global public health and safety, leading to infectious respiratory diseases and causing hundreds of thousands of deaths worldwide every year. New strains are evolved through antigenic shift and drift, thereby developing resistance to existing drugs and vaccines. To address this issue and develop novel antiviral drugs, researchers need to explore new antiviral targets. The genetic products of influenza virus are widely modified through phosphorylation by host kinases. The reversible phosphorylation of serine, threonine, or tyrosine residues dynamically regulates the structures, functions, and subcellular localization of viral proteins at different stages of the viral life cycle. In addition, kinases affect a large number of signaling pathways, which influence virus transmission by regulating the host cell environment, thereby establishing critical virus-host relationships. The dependence on host kinases provides a theoretical basis for developing kinase inhibitors as the next generation of anti-influenza virus drugs. To fully utilize this potential, we need to clarify the influenza virus-host kinase interaction network. The focus of this review is to outline the molecular mechanisms by which host kinases regulate different stages, from adsorption to assembly and budding, in the life cycle of influenza virus. Evaluating the contributions of different host kinases and their specific phosphorylation throughout the influenza virus life cycle can provide a comprehensive overview of the virus-host kinase interaction network, which may help reveal potential targets for developing novel antiviral drugs.

Key words:influenza virus;kinases;life cycle;infection