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

Science 2026

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Authors: Caleb R. Glassman, Kheewoong Baek, Gaopeng Hou, Qiru Zeng, Christopher Nardone, Kate B. Juergens, Eric Fujimura, Colin N. O'Leary, Mamie Z. Li, João A. Paulo, Eric S. Fischer, Siyuan Ding
+2 more J. Wade Harper, Stephen J. Elledge
DOI: 10.1126/science.aec6299
Cited by: 3
References: 118

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 noncanonical ligases that rewire cullin-RING ligase machinery. These diverse strategies of virus-mediated degradation converged on immune-related substrates, including JAK1 and CUL1 β−TrCP , 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.

Fields of Study & Subjects

Ubiquitin and proteasome pathways Protein Degradation and Inhibitors interferon and immune responses

Publication details

Journal / source
Science
Publisher
American Association for the Advancement of Science (AAAS)
Volume
393
Issue
6813
Pages
eaec6299–eaec6299
Publication date
9 July 2026
Language
EN