Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Viruses. 2021 Jan 22;13(2):166. doi: 10.3390/v13020166.
Enteroviruses are among the most common human infectious agents. While infections are often mild, the severe neuropathogenesis associated with recent outbreaks of emerging non-polio enteroviruses, such as EV-A71 and EV-D68, highlights their continuing threat to public health. In recent years, our understanding of how non-polio enteroviruses co-opt cellular pathways has greatly increased, revealing intricate host-virus relationships. In this review, we focus on newly identified mechanisms by which enteroviruses hijack the cellular machinery to promote their replication and spread, and address their potential for the development of host-directed therapeutics. Specifically, we discuss newly identified cellular receptors and their contribution to neurotropism and spread, host factors required for viral entry and replication, and recent insights into lipid acquisition and replication organelle biogenesis. The comprehensive knowledge of common cellular pathways required by enteroviruses could expose vulnerabilities amenable for host-directed therapeutics against a broad spectrum of enteroviruses. Since this will likely include newly arising strains, it will better prepare us for future epidemics. Moreover, identifying host proteins specific to neurovirulent strains may allow us to better understand factors contributing to the neurotropism of these viruses.
肠道病毒是最常见的人类感染病原体之一。虽然感染通常很轻微，但最近新兴非脊髓灰质炎肠道病毒（如 EV-A71 和 EV-D68）的严重神经发病机制突显了它们对公共卫生的持续威胁。近年来，我们对非脊髓灰质炎肠道病毒如何篡夺细胞途径的理解有了很大的提高，揭示了复杂的宿主-病毒关系。在这篇综述中，我们重点讨论了肠道病毒劫持细胞机制以促进其复制和传播的新发现机制，并探讨了它们在开发针对宿主的治疗方法方面的潜力。具体来说，我们讨论了新发现的细胞受体及其对嗜神经和传播的贡献、病毒进入和复制所需的宿主因子，以及最近对脂质获取和复制细胞器发生的深入了解。肠道病毒所需的常见细胞途径的全面知识可能会暴露出针对广泛肠道病毒的宿主导向治疗的弱点。由于这可能包括新出现的菌株，因此它将使我们更好地为未来的流行做好准备。此外，鉴定神经毒力株特有的宿主蛋白可能使我们能够更好地了解导致这些病毒嗜神经的因素。
