近日，哈佛医学院Stephen J. Elledge及其研究组探明病毒体泛素连接酶的发现揭示了免疫逃避的多种机制。该项研究成果发表在2026年7月9日出版的《科学》上。

研究团队应用了一个约10,000个开放阅读框的病毒库来发现病毒泛素连接酶，绘制其降解机制和宿主底物主题靶向CRISPR筛选和蛋白质组学。这些病毒效应物可分为模拟宿主E3的典型连接酶、重定向宿主E3的劫持酶和重新连接Cullin-RING连接酶机制的非典型连接酶。这些不同的病毒介导降解策略聚集在免疫相关底物上，包括JAK1和CUL1βTrCP，强调免疫逃避是病毒泛素连接酶进化的主要驱动因素。他们的发现阐明了利用泛素-蛋白酶体系统的病毒策略，具有潜在的治疗靶向性。

研究人员表示，病毒主题是细胞内的寄生虫，它们重新编程宿主蛋白质组以促进复制和逃避免疫识别。

附：英文原文

Title: Virome-wide ubiquitin ligase discovery reveals diverse mechanisms of immune evasion

Author: Caleb R. Glassman, Kheewoong Baek, Gaopeng Hou, Qiru Zeng, Christopher Nardone, Kate B. Juergens, Eric Fujimura, Colin N. O’Leary, Mamie Z. Li, Joao A. Paulo, Eric S. Fischer, Siyuan Ding, J. Wade Harper, Stephen J. Elledge

Issue&Volume: 2026-07-09

Abstract: Viruses are intracellular parasites that reprogram the host proteome to promote replication and evade immune recognition. We applied a virome-wide library of ~10,000 open reading frames to discover viral ubiquitin ligases, mapping their mechanisms of degradation and host substrates using targeted CRISPR screens and proteomics. These viral effectors could be classified as canonical ligases that mimic host E3s, hijackers that redirect host E3s, and non-canonical ligases that rewire Cullin-RING ligase machinery. These diverse strategies of virus-mediated degradation converged on immune-related substrates, including JAK1 and CUL1βTrCP, underscoring immune evasion as a major driver of viral ubiquitin ligase evolution. Our findings elucidate viral strategies for exploiting the ubiquitin–proteasome system with potential for therapeutic targeting.

DOI: aec6299

Source: https://www.science.org/doi/10.1126/science.aec6299