1. Academic Validation
  2. Repurposing alcohol-abuse drug disulfiram for the treatment of KSHV-infected primary effusion lymphoma by activating antiviral innate immunity

Repurposing alcohol-abuse drug disulfiram for the treatment of KSHV-infected primary effusion lymphoma by activating antiviral innate immunity

  • PLoS Pathog. 2025 Mar 4;21(3):e1012957. doi: 10.1371/journal.ppat.1012957.
Lijie Wang 1 Zhenshan Liu 2 Zeyu Xu 1 Wenjing Wang 1 Jinhong Yang 1 Junjie Zhang 1 Shanping He 1 Qiming Liang 2 Tingting Li 1
Affiliations

Affiliations

  • 1 Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, Laboratory of Animal Nutrition and Human Health, Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China.
  • 2 Shanghai Institute of Immunology, Department of Immunology and Microbiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Abstract

Cancer remains a leading cause of global mortality, characterized by high treatment costs, and generally poor prognoses. Developing new anti-cancer drugs requires substantial investment, extended development timelines, and a high failure rate. Therefore, repurposing existing US Food and Drug Administration (FDA)-approved drugs for Other Diseases as potential anti-cancer therapies offers a faster and more cost-effective approach. Primary effusion lymphoma (PEL) is an aggressive B-cell malignancy linked to Kaposi's sarcoma-associated herpesvirus (KSHV) Infection. In this study, we identified that disulfiram (DSF), an FDA-approved medication for alcohol dependence, acts as a potent inhibitor of KSHV-positive PEL. DSF suppresses PEL cell proliferation by inducing Apoptosis through the activation of innate Antiviral immunity. Remarkably, DSF effectively impedes KSHV reactivation and virion production in both PEL and endothelial cells. Inhibition of TANK binding kinase 1 (TBK1) or interferon regulatory factor 3 (IRF3), essential activators of Antiviral innate immunity, reverses DSF's effects on PEL cell survival and KSHV reactivation. Furthermore, DSF treatment significantly hinders the initiation and progression of PEL tumors in a xenograft mouse model, with this effect was notably abolished by TBK1 depletion. Our findings highlighted DSF as a promising therapeutic agent for targeting persistent KSHV Infection and treating PEL tumors.

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