Deciphering the hepatitis E virus ORF1: Functional domains, protein processing, and patient-derived mutations

Fei Zhang; Ling-Dong Xu; Shiying Wu; Bin Wang; Pinglong Xu; Yao-Wei Huang

doi:10.1016/j.virol.2024.110350

Deciphering the hepatitis E virus ORF1: Functional domains, protein processing, and patient-derived mutations

Virology. 2024 Dec 6:603:110350. doi: 10.1016/j.virol.2024.110350. Online ahead of print.

Authors

Fei Zhang¹, Ling-Dong Xu², Shiying Wu³, Bin Wang⁴, Pinglong Xu⁵, Yao-Wei Huang⁶

Affiliations

¹ 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.
² 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.
³ MOE Laboratory of Biosystems Homeostasis & Protection, Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, 310058, China; College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, 310018, China.
⁴ Guangdong Laboratory for Lingnan Modern Agriculture, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China; State Key Laboratory for Animal Disease Control and Prevention, South China Agricultural University, Guangzhou, 510642, China.
⁵ 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; Cancer Center, Zhejiang University, Hangzhou, 310058, China. Electronic address: [email protected].
⁶ Guangdong Laboratory for Lingnan Modern Agriculture, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China; State Key Laboratory for Animal Disease Control and Prevention, South China Agricultural University, Guangzhou, 510642, China. Electronic address: [email protected].

PMID: 39675187
DOI: 10.1016/j.virol.2024.110350

Abstract

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.

Keywords: Antiviral; Hepatitis E virus; Mutations; ORF1; Processing; RdRp; Replication.

Publication types

Review