Identification of viral SIM-SUMO2-interaction inhibitors for treating primary effusion lymphoma

English version

Autoři: Ling Ding ^aff001; Qing Zhu ^aff001; Feng Zhou ^aff003; Hongsheng Tan ^aff004; Wenjia Xu ^aff005; Chengling Pan ^aff006; Caixia Zhu ^aff001; Yuyan Wang ^aff001; Hong Zhang ^aff004; Wenwei Fu ^aff004; Zhikang Qian ^aff005; Zhenghong Yuan ^aff001; Hongxi Xu ^aff004; Fang Wei ^aff002; Qiliang Cai ^aff001
Působiště autorů: MOE& NHC&CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Science, Shanghai Medical College, Fudan University, Shanghai, P. R. China ^aff001; ShengYushou Center of Cell Biology and Immunology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, P. R. China ^aff002; Baoji Affiliated Hospital of Xi’an Medical University, Baoji & MOE Key Laboratory of Western Resources and Modern Biotechnology, College of Life Sciences, Northwest University, Xi’an, Shaanxi, China ^aff003; School of Pharmacy, Shanghai University of Traditional Chinese Medicine & Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai, China ^aff004; Unit of Herpesvirus and Molecular Virology, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, P. R. China ^aff005; Beijing Computing Center, Beijing Academy of Science and Technology & Beijing Beike Deyuan Bio-Pharm Technology Company, Beijing, P. R. China ^aff006; Expert Workstation, Baoji Central Hospital, Baoji, P. R. China ^aff007
Vyšlo v časopise: Identification of viral SIM-SUMO2-interaction inhibitors for treating primary effusion lymphoma. PLoS Pathog 15(12): e32767. doi:10.1371/journal.ppat.1008174
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.ppat.1008174

Souhrn

Primary effusion lymphoma (PEL) is an aggressive B-cell malignancy without effective treatment, and caused by the infection of Kaposi’s sarcoma-associated herpesvirus (KSHV), predominantly in its latent form. Previously we showed that the SUMO2-interacting motif within the viral latency-associated nuclear antigen (LANA^SIM) is essential for establishment and maintenance of KSHV latency. Here, we developed a luciferase based live-cell reporter system to screen inhibitors selectively targeting the interaction between LANA^SIM and SUMO2. Cambogin, a bioactive natural product isolated from the Garcinia genus (a traditional herbal medicine used for cancer treatment), was obtained from the reporter system screening to efficiently inhibit the association of SUMO2 with LANA^SIM, in turn reducing the viral episome DNA copy number for establishment and maintenance of KSHV latent infection at a low concentration (nM). Importantly, Cambogin treatments not only specifically inhibited proliferation of KSHV-latently infected cells in vitro, but also induced regression of PEL tumors in a xenograft mouse model. This study has identified Cambogin as a novel therapeutic agent for treating PEL as well as eliminating persistent infection of oncogenic herpesvirus.

Klíčová slova:

Cancer treatment – Cytotoxicity – Immunoblotting – Immunoprecipitation – Kaposi's sarcoma-associated herpesvirus – Mouse models – Polymerase chain reaction – Virions

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