A genome wide cDNA screen to identify the hepatitis E virus entry receptor

戊型肝炎病毒（HEV）是一种长期被忽视的RNA病毒，是世界范围内人类急性病毒性肝炎的主要病原体。需要更好地了解病毒的生命周期，包括进入宿主细胞的机制，以确定新的治疗靶点。在这个项目中，我们的目标是采用一种新的筛选系统来识别HEV进入受体。阐明HEV进入允许细胞的受体有助于理解宿主和组织的趋向性，并将扩大对HEV病毒-宿主相互作用和HEV诱导病理的宿主介质的理解。受体鉴定还可以建立易感动物模型来研究病毒生命周期和评估抗病毒治疗方法。此外，病毒进入代表了小分子拮抗剂和引发中和抗体的疫苗的良好验证的治疗靶点。我们将采用一套独特的互补方法，包括一种新的HEV细胞培养系统和来自HEV准许原代人肝细胞的互补cDNA文库，以实现基于cDNA的筛选系统，以鉴定和表征这种人畜共患重要病原体的候选HEV进入受体。

The hepatitis E virus (HEV) is a long-neglected RNA virus and the major causative agent of acute viral hepatitis in humans worldwide. A better understanding of the viral life cycle, including the mechanisms of entry into host cells, is needed to identify novel therapeutic targets. In this project we aim to employ a novel screening system to identify HEV entry receptors. Elucidating the receptor which HEV employs to enter permissive cells is instrumental to understanding host and tissue tropism, and will expand the understanding of HEV virus-host interactions and host mediators of HEV induced pathology. Receptor identification can also allow generation of susceptible animal models to study the viral life cycle and evaluate antiviral therapeutics. Furthermore, viral entry represents a well-validated therapeutic target for both small-molecule antagonists and vaccines that elicit neutralizing antibodies. We will employ a set of unique complementary methodologies including a novel HEV cell culture system and a complementary cDNA library derived from HEV-permissive primary human hepatocytes to implement a cDNA-based screening system to identify and characterize candidate HEV entry receptors for this zoonotic important pathogen.