戊型肝炎病毒 ORF1 非结构多聚蛋白的加工过程

IF 2 Q4 VIROLOGY Frontiers in virology Pub Date : 2023-12-08 DOI:10.3389/fviro.2023.1327745
Yogesh A. Karpe
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摘要

戊型肝炎病毒(HEV)开放阅读框 1(ORF1)编码一种非结构性多聚蛋白。在动物体内发现的大多数正义 RNA 病毒中,这种非结构性多聚蛋白都会被病毒蛋白酶或宿主蛋白酶裂解。然而,HEV 多聚蛋白的加工机制仍是 HEV 生物学中最具争议的问题之一。假定的 HEV 蛋白酶在加工过程中的作用难以证明。最近的研究质疑 HEV 蛋白酶的存在,并认为 pORF1 缺乏蛋白酶活性。相反,也有研究表明,参与血液凝固级联的宿主蛋白酶(如凝血酶)在处理 HEV pORF1 多聚蛋白中发挥作用。总之,最近的研究支持 pORF1 缺乏蛋白酶活性、宿主蛋白酶负责处理 pORF1 的观点。本综述全面概述了有关 HEV 的木瓜蛋白酶样半胱氨酸蛋白酶(PCP)的争议性研究,并重点介绍了该领域的最新进展。我们旨在讨论该领域的挑战和机遇,以聚焦于进一步的研究。
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Processing of the Hepatitis E virus ORF1 nonstructural polyprotein

Hepatitis E viruses (HEV) Open Reading Frame 1 (ORF1) encodes a non-structural polyprotein. In most positive-sense RNA viruses found in animals, this non-structural polyprotein is cleaved by viral protease or host protease. However, the mechanism behind the processing of HEV polyprotein remains one of the most controversial questions in HEV biology. The role of putative HEV protease in processing is difficult to demonstrate. Recent studies have questioned the existence of HEV protease and suggested that pORF1 lacks protease activity. Conversely, studies also suggested the role of host proteases involved in the blood coagulation cascade, like thrombin, in processing the HEV pORF1 polyprotein. In summary, recent studies support the notion that pORF1 lacks protease activity and host proteases are responsible for processing pORF1. The present review compiles a thorough overview of contentious research on HEV’s papain-like cysteine protease (PCP) and highlights recent advancements in the field. We aim to discuss the challenges and opportunities in the field to focus on further research.

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