戊型肝炎病毒衣壳蛋白形成淀粉样纤维，隔离TANK结合激酶1以抑制抗病毒反应
The hepatitis E virus capsid protein forms amyloid-like fibrils that sequester TANK-binding kinase 1 to dampen antiviral responses.
摘要(中文译文)
戊型肝炎病毒（HEV）是全球病毒性肝炎的主要病因。我们发现，HEV ORF2衣壳蛋白的N端含有内在无序区（IDRs），这些区域在体外和细胞内均可通过液-液相分离促进凝聚体形成。利用对HEV感染细胞的关联光镜与电镜/电子断层扫描技术，我们观察到ORF2形成由有序堆叠的管状丝状结构组成的高级组装体，类似于淀粉样纤维。通过光镜，我们在多种HEV感染的细胞类型中检测到ORF2纤维，包括人诱导多能干细胞来源的肝细胞和神经元。此外，我们发现中心衔接蛋白TANK结合激酶1被ORF2纤维隔离，从而实现免疫逃逸并增强病毒复制。总之，我们的研究揭示了一种此前未被认识的HEV调控宿主防御通路的机制，并将HEV归入日益增多的利用动态相行为作为调控病毒-宿主相互作用更广泛策略的病毒之列。
Abstract
Hepatitis E virus (HEV) is the leading cause of viral hepatitis worldwide. We find that the HEV ORF2 capsid protein contains intrinsically disordered regions (IDRs) at its N terminus that promote condensate formation through liquid-liquid phase separation both in vitro and in cellulo. Using correlative light and electron microscopy/tomography of HEV-infected cells, we observe that ORF2 forms higher order assemblies composed of orderly stacked tubular filaments resembling amyloid fibrils. By light microscopy, we detect ORF2 fibrils in multiple HEV-infected cell types, including human induced pluripotent stem cell-derived hepatocytes and neurons. Moreover, we discover that the central adapter protein TANK-binding kinase 1 is sequestered by ORF2 fibrils, thereby enabling immune evasion and enhancing viral replication. Together, our findings uncover a previously unrecognized mechanism by which HEV modulates host defense pathways and place HEV among the growing repertoire of viruses that exploit dynamic phase behavior as a broader strategy to regulate virus-host interactions.
如何引用
AMA
Paula Jordan, Jungen Hu, Giulia Mizzon, Paola Agüero-Gamboa, Chiara Olmeo, Debin Tian, et al. The hepatitis E virus capsid protein forms amyloid-like fibrils that sequester TANK-binding kinase 1 to dampen antiviral responses.. Cell reports. 2026; doi:10.1016/j.celrep.2026.117513.
APA
Paula Jordan, Jungen Hu, Giulia Mizzon, Paola Agüero-Gamboa, Chiara Olmeo, Debin Tian, et al (2026). The hepatitis E virus capsid protein forms amyloid-like fibrils that sequester TANK-binding kinase 1 to dampen antiviral responses.. Cell reports. https://doi.org/10.1016/j.celrep.2026.117513
GB/T 7714
Paula Jordan, Jungen Hu, Giulia Mizzon, Paola Agüero-Gamboa, Chiara Olmeo, Debin Tian, et al. The hepatitis E virus capsid protein forms amyloid-like fibrils that sequester TANK-binding kinase 1 to dampen antiviral responses.[J]. Cell reports, 2026 doi:10.1016/j.celrep.2026.117513.
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