Abstract
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 antitumor agents that 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. Quantitative PCR (qPCR) and cytofluorometry assays were used for detecting both viral DNA and the latency factor LANA (latency-associated nuclear antigen) in BC3 cells, respectively. The capacity of sulfonamides to impair MDM2–p53 complex formation was detected by an enzyme-linked immunosorbent assay method. The analysis of variance was performed according to one-way analysis of variance 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 that 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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Acknowledgements
We thank Ms Sally Davies for helping in the preparation and correction of the manuscript. This work was supported by Fondazione Banco di Sardegna 2014-15 and US Public Health Service Grant DE018304 to DPD.
Author contributions
RP, AI and DPD designed and wrote the paper; FA, EP and SU performed reverse transcription–PCR and enzyme-linked immunosorbent assays; CM, RS, RB and WC performed all the fluorescence and cytofluorometry tests.
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Angius, F., Piras, E., Uda, S. et al. Antimicrobial sulfonamides clear latent Kaposi sarcoma herpesvirus infection and impair MDM2–p53 complex formation. J Antibiot 70, 962–966 (2017). https://doi.org/10.1038/ja.2017.67
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DOI: https://doi.org/10.1038/ja.2017.67
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