کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
3426740 | 1227342 | 2007 | 18 صفحه PDF | دانلود رایگان |
This study describes the mechanism of antiviral action of the N-aminoimidazole derivatives which exclusively inhibit retroviruses such as HIV-1, HIV-2, SIV and MSV. These antiretroviral compounds, with lead prototype NR-818, were found to inhibit HIV-1 replication at the transcriptional level. Analysis of each individual step of viral transcription, including transcriptional activation mediated by NF-κB, the chromatin remodeling process at the viral promoter and viral mRNA transcription mediated by RNAPII, showed that NR-818 was able to prolong the binding of NF-κB to its consensus sequence. The compound also increased the acetylation of histones H3 and H4 within the nucleosome nuc-1 at the transcription initiation site and inhibited the recruitment of viral Tat and the phosphorylation of the RNA polymerase II C-terminal domain (RNAPII CTD) at the viral promoter upon stimulation of latently HIV-1-infected cell lines. As a result, viral mRNA expression and subsequent viral p24 production in stimulated latently HIV-1-infected cell lines was suppressed by NR-818. These data suggest that the N-aminoimidazole derivatives effectively inhibit the reactivation of HIV-1 and may contribute to the control of the latent HIV-1 reservoir.
Journal: Virology - Volume 365, Issue 1, 15 August 2007, Pages 220–237