کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5675046 1594209 2017 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Calcein represses human papillomavirus 16 E1-E2 mediated DNA replication via blocking their binding to the viral origin of replication
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ویروس شناسی
پیش نمایش صفحه اول مقاله
Calcein represses human papillomavirus 16 E1-E2 mediated DNA replication via blocking their binding to the viral origin of replication
چکیده انگلیسی


- The TopBP1 interacting drug calcein blocks HPV16 E1-E2 DNA replication at relatively non-toxic doses.
- The block is due to the inability of viral replication factors to interact with the origin in the presence of calcein.
- Calcein does not affect the ability of E2 to regulate transcription, nor to bind transcriptional control regions.
- Overall the results demonstrate that calcein is a promising lead as a drug that could selectively target HPV16 DNA replication.

Human papillomaviruses are causative agents in several human diseases ranging from genital warts to ano-genital and oropharyngeal cancers. Currently only symptoms of HPV induced disease are treated; there are no antivirals available that directly target the viral life cycle. Previously, we determined that the cellular protein TopBP1 interacts with the HPV16 replication/transcription factor E2. This E2-TopBP1 interaction is essential for optimal E1-E2 DNA replication and for the viral life cycle. The drug calcein disrupts the interaction of TopBP1 with itself and other host proteins to promote cell death. Here we demonstrate that calcein blocks HPV16 E1-E2 DNA replication via blocking the viral replication complex forming at the origin of replication. This occurs at non-toxic levels of calcein and demonstrates specificity as it does not block the ability of E2 to regulate transcription. We propose that calcein or derivatives could be developed as an anti-HPV therapeutic.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Virology - Volume 508, August 2017, Pages 180-187
نویسندگان
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