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0This research article describes a high-throughput pooled genetic screen designed to identify viral proteins, termed "degradins," that manipulate the host’s ubiquitin-proteasome system to facilitate infection. By testing a library of approximately 10,000 viral open reading frames, the study discovered various mechanisms that viruses use to bypass or hijack host immune responses. The authors categorized these viral ubiquitin ligases into canonical, noncanonical, and hijacker classes based on how they interface with host Cullin-RING ligases. Detailed structural and proteomic analyses revealed that these diverse viral strategies often converge on the same antiviral signaling pathways, such as those involving JAK1 or IRF3. Ultimately, the findings provide a comprehensive map of how pathogens rewire cellular physiology to achieve immune evasion. These insights offer a foundation for developing new therapeutic interventions that target viral exploitation of protein degradation machinery.
References:
Glassman C R, Baek K, Hou G, et al. Virome-wide ubiquitin ligase discovery reveals diverse mechanisms of immune evasion[J]. Science, 2026.
