ArticlePLoS pathogens2024
Non-canonical regulation of the reactivation of an oncogenic herpesvirus by the OTUD4-USP7 deubiquitinases.
Article in PLoS pathogens, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
9 citing papers in PubMed, 9 citations in OpenAlex.
- SUMOylation and ubiquitination reciprocally regulate SMCHD1 antiviral activity against herpes simplex virus 1.PLoS pathogens · 2026Article
- Article
- OTUD4 suppresses colorectal cancer progression through deubiquitinating p53.Discover oncology · 2025Article
- USP7-mediated stabilization of CXCL3 aggravates inflammation in models of acute lung injury.Journal of thoracic disease · 2025Article
- IRF1 amplifies HSV-1-triggered antiviral innate immunity in a feed-forward manner.Cell insight · 2025Article
- Viral pseudo-enzyme facilitates KSHV lytic replication via suppressing PFAS-mediated RTA deamidation.Virologica Sinica · 2025Article
- Ubiquitin-dependent proteasomal degradation of small hepatitis B virus surface antigen mediated by TRIM21 and antagonized by OTUD4.Journal of virology · 2025Article
- Disrupting the OTUD4-USP7 deubiquitinase complex to suppress herpesvirus replication: a novel antiviral strategy.PLoS pathogens · 2025Article
- Palmitoylation of KSHV pORF55 is required for Golgi localization and efficient progeny virion production.PLoS pathogens · 2024Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
Deubiquitinases (DUBs) remove ubiquitin from substrates and play crucial roles in diverse biological processes. However, our understanding of deubiquitination in viral replication remains limited. Employing an oncogenic human herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) to probe the role of protein deubiquitination, we found that Ovarian tumor family deubiquitinase 4 (OTUD4) promotes KSHV reactivation. OTUD4 interacts with the replication and transcription activator (K-RTA), a key transcription factor that controls KSHV reactivation, and enhances K-RTA stability by promoting its deubiquitination. Notably, the DUB activity of OTUD4 is not required for K-RTA stabilization; instead, OTUD4 functions as an adaptor protein to recruit another DUB, USP7, to deubiquitinate K-RTA and facilitate KSHV lytic reactivation. Our study has revealed a novel mechanism whereby KSHV hijacks OTUD4-USP7 deubiquitinases to promote lytic reactivation, which could be potentially harnessed for the development of new antiviral therapies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.