Identification of viral SIM-SUMO2-interaction inhibitors for treating primary effusion lymphoma.
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-associa...
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2019-12-01
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Online Access: | https://doi.org/10.1371/journal.ppat.1008174 |
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doaj-54825f9bb7c24875aa2ad7ac77e4d6ef2021-04-21T17:08:59ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742019-12-011512e100817410.1371/journal.ppat.1008174Identification of viral SIM-SUMO2-interaction inhibitors for treating primary effusion lymphoma.Ling DingQing ZhuFeng ZhouHongsheng TanWenjia XuChengling PanCaixia ZhuYuyan WangHong ZhangWenwei FuZhikang QianZhenghong YuanHongxi XuFang WeiQiliang CaiPrimary 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 (LANASIM) 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 LANASIM 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 LANASIM, 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.https://doi.org/10.1371/journal.ppat.1008174 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ling Ding Qing Zhu Feng Zhou Hongsheng Tan Wenjia Xu Chengling Pan Caixia Zhu Yuyan Wang Hong Zhang Wenwei Fu Zhikang Qian Zhenghong Yuan Hongxi Xu Fang Wei Qiliang Cai |
spellingShingle |
Ling Ding Qing Zhu Feng Zhou Hongsheng Tan Wenjia Xu Chengling Pan Caixia Zhu Yuyan Wang Hong Zhang Wenwei Fu Zhikang Qian Zhenghong Yuan Hongxi Xu Fang Wei Qiliang Cai Identification of viral SIM-SUMO2-interaction inhibitors for treating primary effusion lymphoma. PLoS Pathogens |
author_facet |
Ling Ding Qing Zhu Feng Zhou Hongsheng Tan Wenjia Xu Chengling Pan Caixia Zhu Yuyan Wang Hong Zhang Wenwei Fu Zhikang Qian Zhenghong Yuan Hongxi Xu Fang Wei Qiliang Cai |
author_sort |
Ling Ding |
title |
Identification of viral SIM-SUMO2-interaction inhibitors for treating primary effusion lymphoma. |
title_short |
Identification of viral SIM-SUMO2-interaction inhibitors for treating primary effusion lymphoma. |
title_full |
Identification of viral SIM-SUMO2-interaction inhibitors for treating primary effusion lymphoma. |
title_fullStr |
Identification of viral SIM-SUMO2-interaction inhibitors for treating primary effusion lymphoma. |
title_full_unstemmed |
Identification of viral SIM-SUMO2-interaction inhibitors for treating primary effusion lymphoma. |
title_sort |
identification of viral sim-sumo2-interaction inhibitors for treating primary effusion lymphoma. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Pathogens |
issn |
1553-7366 1553-7374 |
publishDate |
2019-12-01 |
description |
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 (LANASIM) 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 LANASIM 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 LANASIM, 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. |
url |
https://doi.org/10.1371/journal.ppat.1008174 |
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