Efficient lytic induction of kaposi’s sarcoma-associated herpesvirus (KSHV) by the anthracyclines
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Hyunju Kang1,11,*, Jaehyung Song3,*, Kwangman Choi1,4,*, Hyeongki Kim1,2, Miri Choi1, So-Young Lee5, Chonsaeng Kim6, Sang Jun Lee7, Moon Jung Song8, Hyojeung Kang9, Sung Hoon Back10, Sang-Bae Han11 and Sungchan Cho1,2
1 Targeted Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongwon, Chungbuk, Republic of Korea
2 Department of Biomolecular Science, University of Science and Technology, Daejeon, Republic of Korea
3 College of Pharmacy, Kangwon National University, Chuncheon, Republic of Korea
4 Department of Medical Biotechnology, Soonchunhyang University, Asan, Republic of Korea
5 International Cooperation Office, Ministry of Food & Drug Safety, Cheongwon, Chungbuk, Republic of Korea
6 Virus Research and Testing Group, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea
7 Infection and Immunity Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea
8 Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea
9 College of Pharmacy, Research Institute of Pharmaceutical Sciences, and Institute for Microorganisms, Kyungpook National University, Daegu, Republic of Korea
10 School of Biological Sciences, University of Ulsan, Ulsan, Republic of Korea
11 College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea
* These authors contributed equally to this work
Sungchan Cho, email:
Keywords: Kaposi’s sarcoma-associated herpesvirus (KSHV), Lytic induction, Anthracyclines, Apoptosis, DNA intercalation
Received: July 16, 2014 Accepted: August 09, 2014 Published: August 10, 2014
Lytic induction of latent Kaposi’s sarcoma-associated herpesvirus (KSHV) has been considered as a therapeutic option for efficient treatment of several KSHV-associated malignancies. Here, we developed a robust high-throughput screening system that allows an easy and quantitative measurement of lytic induction of latent KSHV and discovered three anthracyclines as potent inducers from screen of FDA-approved drugs. Lytic induction of latent KSHV by three compounds was verified by the significant induction of lytic genes and subsequent production of infectious KSHV. Importantly, lytic induction by three compounds was much more efficient than that by sodium butyrate, a well-characterized inducer of KSHV lytic cycle. Mechanistically, the anthracyclines caused lytic induction of KSHV through apoptosis induced by their DNA intercalation rather than topoisomerase II inhibition. Consequently, our results clearly demonstrated a role of anthracyclines as effective lytic inducers of KSHV and also provided a molecular basis of their use for efficient treatment of diseases associated with KSHV infection.
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