National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, Hubei Key Laboratory of Industrial Microbiology, Sino-German Biomedical Center, Hubei University of Technology, Wuhan, China.
National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, Hubei Key Laboratory of Industrial Microbiology, Sino-German Biomedical Center, Hubei University of Technology, Wuhan, China.
Lab Invest. 2024 Feb;104(2):100298. doi: 10.1016/j.labinv.2023.100298. Epub 2023 Nov 25.
Enterovirus A71 (EV-A71) is one of the major causative agents of hand, foot, and mouth disease (HFMD) that majorly affects children. Most of the time, HFMD is a mild disease but can progress to severe complications, such as meningitis, brain stem encephalitis, acute flaccid paralysis, and even death. HFMD caused by EV-A71 has emerged as an acutely infectious disease of highly pathogenic potential in the Asia-Pacific region. In this review, we introduced the properties and life cycle of EV-A71, and the pathogenesis and the pathophysiology of EV-A71 infection, including tissue tropism and host range of virus infection, the diseases caused by the virus, as well as the genes and host cell immune mechanisms of major diseases caused by enterovirus 71 (EV-A71) infection, such as encephalitis and neurologic pulmonary edema. At the same time, clinicopathologic characteristics of EV-A71 infection were introduced. There is currently no specific medication for EV-A71 infection, highlighting the urgency and significance of developing suitable anti-EV-A71 agents. This overview also summarizes the targets of existing anti-EV-A71 agents, including virus entry, translation, polyprotein processing, replication, assembly and release; interferons; interleukins; the mitogen-activated protein kinase, phosphatidylinositol 3-kinase, and protein kinase B signaling pathways; the oxidative stress pathway; the ubiquitin-proteasome system; and so on. Furthermore, it overviews the effects of natural products, monoclonal antibodies, and RNA interference against EV-A71. It also discusses issues limiting the research of antiviral drugs. This review is a systematic and comprehensive summary of the mechanism and pathological characteristics of EV-A71 infection, the latest progress of existing anti-EV-A71 agents. It would provide better understanding and guidance for the research and application of EV-A71 infection and antiviral inhibitors.
肠道病毒 A71（EV-A71）是引起手足口病（HFMD）的主要病原体之一，主要影响儿童。大多数情况下，HFMD 是一种轻度疾病，但可进展为严重并发症，如脑膜炎、脑干脑炎、急性弛缓性麻痹，甚至死亡。肠道病毒 A71（EV-A71）引起的手足口病已成为亚太地区具有高致病性潜力的急性传染病。在这篇综述中，我们介绍了 EV-A71 的特性和生命周期，以及 EV-A71 感染的发病机制和病理生理学，包括病毒感染的组织嗜性和宿主范围、病毒引起的疾病，以及肠道病毒 71（EV-A71）感染引起的主要疾病的基因和宿主细胞免疫机制，如脑炎和神经肺水肿。同时，介绍了 EV-A71 感染的临床病理特征。目前，EV-A71 感染尚无特效药物，这凸显了开发合适的抗 EV-A71 药物的紧迫性和重要性。本综述还总结了现有抗 EV-A71 药物的作用靶点，包括病毒进入、翻译、多蛋白加工、复制、组装和释放；干扰素；白细胞介素；有丝分裂原激活蛋白激酶、磷脂酰肌醇 3-激酶和蛋白激酶 B 信号通路；氧化应激途径；泛素-蛋白酶体系统等。此外，还综述了天然产物、单克隆抗体和 RNA 干扰对 EV-A71 的作用。还讨论了限制抗病毒药物研究的问题。这篇综述是对 EV-A71 感染机制和病理特征、现有抗 EV-A71 药物最新进展的系统和全面总结。它将为 EV-A71 感染和抗病毒抑制剂的研究和应用提供更好的理解和指导。
