Efficient lytic induction of kaposi's sarcoma-associated herpesvirus (KSHV) by the anthracyclines = Anthracycline에 의한 카포시 싸코마 바이러스의 용해 재활성 유도

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Title
Efficient lytic induction of kaposi's sarcoma-associated herpesvirus (KSHV) by the anthracyclines = Anthracycline에 의한 카포시 싸코마 바이러스의 용해 재활성 유도
Author(s)
Hyunju Kang; J Song; Kwangman Choi; Hyeongki Kim; Miri Choi; S Y Lee; C Kim; Sang Jun Lee; M J Song; H Kang; S H Back; S B Han; Sungchan Cho
Bibliographic Citation
Oncotarget, vol. 5, no. 18, pp. 8515-8527
Publication Year
2014
Abstract
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.
Keyword
AnthracyclinesApoptosisDNA intercalationKaposi's sarcoma-associated herpesvirus (KSHV)Lytic induction
ISSN
1949-2553
Publisher
Impact Journals
DOI
http://dx.doi.org/10.18632/oncotarget.2335
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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