Journal info
|
||
Select Journal
Journals
Bratislava Medical Journal Endocrine Regulations General Physiology and Biophysics Neoplasma Acta Virologica Current articles 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 Studia Psychologica Cardiology Letters Psychológia a patopsych. dieťaťa Kovove Materialy-Metallic Materials Slovenská hudbaWebshop Cart
Acta Virologica Vol.59, No.1, p.64-77, 2015 |
||
Title: Indole derivatives inhibit hepatitis C virus replication through induction of pro-inflammatory cytokines | ||
Author: S. Lee, G. Jin, D. Kim, S. Son, K. Lee, C. Lee | ||
Abstract: Previously, we discovered a series of indole derivatives as a new class of hepatitis C virus (HCV) replication inhibitors by using a target-free chemical genetic strategy. Through a structure-activity relationship study, the compound 12e was identified as the most potent inhibitor of this class (EC50 = 1.1 μmol/l) with minimal cytotoxicity (CC50 = 61.8 μmol/l). In order to gain insight into its detailed antiviral mechanism of action, we performed PCR array analyses and found that 12e was able to activate transcription of a number of pro-inflammatory as well as antiviral cytokine genes including CXCL-8, IL-1α, TNF-α, IL-3, IRAK-1, and DDX58. Their induction by 12e was verified by individual RT-PCR analyses. In addition, 12e was found to stimulate secretion of soluble factors with anti-HCV replication activity. Among the 12e-induced pro-inflammatory cytokines, CXCL-8 showed a strong positive correlation between its transcriptional activation and antiviral potency. Interestingly, a recombinant CXCL-8 protein also reduced HCV replication, though only moderately. In conclusion, we found a novel mode of action of indole derivatives in inhibiting HCV replication, particularly the induction of pro-inflammatory cytokines. |
||
Keywords: hepatitis C virus; indole derivatives; replication inhibitors; CXCL-8; pro-inflammatory cytokines; transcriptional activation | ||
Year: 2015, Volume: 59, Issue: 1 | Page From: 64, Page To: 77 | |
doi:10.4149/av_2015_01_64 |
||
|
download file |
|