Department for Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany.
Department of Infectious Diseases and Virology, Heidelberg University Hospital, Cluster of Excellence CellNetworks, Heidelberg, Germany.
Hepatology. 2023 Jun 1;77(6):2104-2117. doi: 10.1097/HEP.0000000000000308. Epub 2023 Feb 7.
Being the most common cause of acute viral hepatitis with >20 million cases per year and 70,000 deaths annually, HEV presents a long-neglected and underinvestigated health burden. Although the entry process of viral particles is an attractive target for pharmacological intervention, druggable host factors to restrict HEV entry have not been identified so far.
Here we identify the EGF receptor (EGFR) as a novel host factor for HEV and reveal the significance of EGFR for the HEV entry process. By utilizing RNAi, chemical modulation with Food and Drug Administration-approved drugs, and ectopic expression of EGFR, we revealed that EGFR is critical for HEV infection without affecting HEV RNA replication or assembly of progeny virus. We further unveiled that EGFR itself and its ligand-binding domain, rather than its signaling function, is responsible for the proviral effect. Modulation of EGF expression in HepaRG cells and primary human hepatocytes affected HEV infection.
Taken together, our study provides novel insights into the life cycle of HEV and identified EGFR as a possible target for future antiviral strategies against HEV.
戊型肝炎病毒（HEV）是全球最常见的急性病毒性肝炎病因之一，每年导致超过 2000 万例病例和 7 万例死亡，但目前仍被严重忽视和研究不足。尽管病毒颗粒的进入过程是药物干预的一个有吸引力的靶点，但迄今为止尚未发现能够限制 HEV 进入的可成药的宿主因子。
本研究鉴定出表皮生长因子受体（EGFR）是 HEV 的一种新型宿主因子，并揭示了 EGFR 对 HEV 进入过程的重要性。通过利用 RNAi、经食品和药物管理局批准的药物进行化学调节以及 EGFR 的异位表达，我们揭示了 EGFR 对于 HEV 感染是至关重要的，而不会影响 HEV RNA 复制或子代病毒的组装。我们进一步揭示了 EGFR 本身及其配体结合域而非其信号功能负责促进病毒感染。HepaRG 细胞和原代人肝细胞中 EGF 表达的调节影响了 HEV 感染。
综上所述，本研究为 HEV 的生命周期提供了新的见解，并将 EGFR 鉴定为针对 HEV 的未来抗病毒策略的潜在靶点。
