کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8523232 | 1557789 | 2018 | 38 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
BET bromodomain inhibitors show anti-papillomavirus activity in vitro and block CRPV wart growth in vivo
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موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ویروس شناسی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Bromodomain and Extra-Terminal domain (BET) proteins are host proteins which regulate gene transcription, they bind acetylated lysine residues in histones and non-histone proteins via bromodomains, functioning as scaffold proteins in the formation of transcriptional complexes at gene regulatory regions. The BET protein BRD4 has been shown to be involved in the papillomavirus life cycle, as a co-factor for viral E2 and also mediating viral partitioning in some virus types. We set out to study the activity of small molecule BET bromodomain inhibitors in models of papillomavirus infection. Several BET inhibitors reduced HPV11 E1ËE4 mRNA expression in vitro and topical therapeutic administration of an exemplar compound I-BET762, abrogated CRPV cutaneous wart growth in rabbits, demonstrating translation of anti-viral effects to efficacy in vivo. Additionally I-BET762 markedly reduced viability of HPV16 infected W12â¯cells compared to non-infected C33A cells. The molecular mechanism for the cytotoxicity to W12â¯cells is unknown but may be through blocking viral-dependent cell-survival factors. We conclude that these effects, across multiple papillomavirus types and in vivo, highlight the potential to target BET bromodomains to treat HPV infection.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Antiviral Research - Volume 154, June 2018, Pages 158-165
Journal: Antiviral Research - Volume 154, June 2018, Pages 158-165
نویسندگان
Mary A. Morse, Karla K. Balogh, Sarah A. Brendle, Colin A. Campbell, Mao X. Chen, Rebecca C. Furze, Isobel L. Harada, Ian D. Holyer, Umesh Kumar, Kevin Lee, Rab K. Prinjha, Martin Rüdiger, Jonathan T. Seal, Simon Taylor, Jason Witherington,