Zhang Fei, Xu Ling-Dong, Wu Shiying, Wang Bin, Xu Pinglong, Huang Yao-Wei
Department of Hepatobiliary and Pancreatic Surgery and Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China; ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, 311215, China; MOE Laboratory of Biosystems Homeostasis & Protection, Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, 310058, China.
Department of Hepatobiliary and Pancreatic Surgery and Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China; MOE Laboratory of Biosystems Homeostasis & Protection, Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, 310058, China; Laboratory Animal Center, Zhejiang University, Hangzhou, 310058, China.
Virology. 2025 Feb;603:110350. doi: 10.1016/j.virol.2024.110350. Epub 2024 Dec 6.
Hepatitis E virus (HEV) is a major cause of acute and chronic hepatitis in humans. The HEV open reading frames (ORF1) encodes a large non-structural protein essential for viral replication, which contains several functional domains, including helicase and RNA-dependent RNA polymerase. A confusing aspect is that, while RNA viruses typically encode large polyproteins that rely on their enzymatic activity for processing into functional units, the processing of the ORF1 protein and the mechanisms involved remain unclear. The ORF1 plays a pivotal role in the viral life cycle, thus mutations in this region, especially those occurring under environmental pressures such as during antiviral drug treatment, could significantly affect viral replication and survival. Here, we summarize the recent advances in the functional domains, processing, and mutations of ORF1. Gaining a deeper understanding of HEV biology, particularly focusing on ORF1, could facilitate the development of new strategies to control HEV infections.
戊型肝炎病毒（HEV）是人类急性和慢性肝炎的主要病因。HEV开放阅读框（ORF1）编码一种对病毒复制至关重要的大型非结构蛋白，该蛋白包含几个功能域，包括解旋酶和RNA依赖性RNA聚合酶。一个令人困惑的方面是，虽然RNA病毒通常编码大型多聚蛋白，这些多聚蛋白依靠其酶活性加工成功能单元，但ORF1蛋白的加工过程及相关机制仍不清楚。ORF1在病毒生命周期中起关键作用，因此该区域的突变，尤其是在抗病毒药物治疗等环境压力下发生的突变，可能会显著影响病毒的复制和存活。在此，我们总结了ORF1在功能域、加工过程和突变方面的最新进展。更深入地了解HEV生物学，尤其是聚焦于ORF1，可能有助于开发控制HEV感染的新策略。
