2. Academic Validation
  3. Disrupting the OTUD4-USP7 deubiquitinase complex to suppress herpesvirus replication: a novel antiviral strategy

Disrupting the OTUD4-USP7 deubiquitinase complex to suppress herpesvirus replication: a novel antiviral strategy

  • PLoS Pathog. 2025 Apr 10;21(4):e1013052. doi: 10.1371/journal.ppat.1013052.
Shaowei Wang 1 2 3,  Xuezhang Tian 1 2,  Yunhong Zhong 1 2,  Xiaoyu Xie 4 5,  Ming Gao 1 2,  Chuchu Zhang 1 2,  Xi Cheng 1 2,  Yining Qi 1 2,  Bo Zhong 2 6,  Pinghui Feng 7,  Ke Lan 2 8,  Junjie Zhang 1 2 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, State Key Laboratory of Virology and Biosafety, Medical Research Institute, Wuhan University, Wuhan, China.
  • 2 Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Wuhan University, Wuhan, China.
  • 3 Hubei Key Laboratory of Tumor Biological Behavior, Zhongnan Hospital of Wuhan University, Wuhan, China.
  • 4 Department of Colorectal and Anal Surgery, Clinical Center of Intestinal and Colorectal Diseases of Hubei Province, Zhongnan Hospital of Wuhan University, Wuhan, China.
  • 5 Hubei Key Laboratory of Intestinal and Colorectal Diseases, Zhongnan Hospital of Wuhan University, Wuhan, China.
  • 6 Department of Gastrointestinal Surgery, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.
  • 7 Section of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California, United States of America.
  • 8 State Key Laboratory of Virology, School of Life Sciences, Wuhan University, Wuhan, China.
PMID: 40208866 DOI: 10.1371/journal.ppat.1013052
Abstract

The development of effective and broad-spectrum Antiviral therapies remains an unmet need. Current virus-targeted Antiviral strategies are often limited by narrow spectrum of activity and the rapid emergence of resistance. As a result, there is increasing interest in alternative approaches that target host cell factors critical for viral replication. One promising strategy is the targeting of deubiquitinases (DUBs), Enzymes that regulate key host and Viral Proteins involved in viral reactivation and replication. In this study, we explore the potential of targeting a DUB complex for Antiviral therapy based on our previous study. Our previous work revealed that the OTUD4-USP7 DUB complex plays a crucial role in KSHV lytic reactivation. Here, we developed a peptide, p8, which effectively disrupts the interaction between OTUD4 and USP7, leading to decreased abundance of the key viral transcription factor, RTA, and suppression of murine herpesvirus replication in vivo. These findings underscore the OTUD4-USP7 DUB complex as a promising host-targeting Antiviral therapeutic target for the treatment of KSHV-associated malignancies. Moreover, our study highlights the potential of DUB-targeting therapies as a novel and effective strategy for the development of broad-spectrum Antiviral agents.

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