Antimicrobial sulfonamides clear latent Kaposi sarcoma herpesvirus infection and impair MDM2-p53 complex formation.

Antimicrobial sulfonamides clear latent Kaposi sarcoma herpesvirus infection and impair MDM2-p53 complex formation.
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DOI:
10.1038/ja.2017.67
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发表时间:
2017-08
期刊:
The Journal of antibiotics
影响因子:
--
通讯作者:
Ingianni A
Ingianni A
中科院分区:
其他
文献类型:
--
作者:
Angius F;Piras E;Uda S;Madeddu C;Serpe R;Bigi R;Chen W;Dittmer DP;Pompei R;Ingianni A

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Kaposi Sarcoma Herpesvirus (KSHV), also known as Human Herpesvirus 8, is the causative agent of Kaposi sarcoma; this malignant angiosarcoma is usually treated with conventional anti-tumor agents, which can control disease evolution, but do not clear the latent KSHV episome that binds to cellular DNA. Some commercial antibacterial sulfonamides were tested for the ability to suppress latent KSHV. qPCR and cytofluorometry assays were used for detecting both viral DNA and the latency factor LANA in BC3 cells, respectively. The capacity of sulfonamides to impair MDM2-p53 complex formation was detected by an ELISA method. The analysis of variance was performed according to one-way ANOVA with Fisher as a post-hoc test. Here we show that sulfonamide antibiotics are able to suppress the KSHV latent state in permanently-infected BC3 lymphoma-cells and interfere with the formation of the MDM2-p53 complex, which KSHV seemingly needs to support latency and to trigger tumor cell transformation. These findings detected a new molecular target for the activity of sulfonamides and offer a new potential perspective for treating KSHV-induced lymphoproliferative diseases.
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