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Title: Inhibition of human immunodeficiency virus type 1 transcription by N-aminoimidazole derivatives
Authors: Stevens, Miguel ×
Balzarini, Jan
Lagoja, Irene M
Noppen, Bernard
Fran├žois, Katrien
Van Aerschot, Arthur
Herdewijn, Piet
De Clercq, Erik
Pannecouque, Christophe #
Issue Date: Aug-2007
Series Title: Virology vol:365 issue:1 pages:220-237
Abstract: 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-kappaB, 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-kappaB 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.
URI: 
ISSN: 0042-6822
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
Molecular and Vascular Biology
Medicinal Chemistry (Rega Institute)
× corresponding author
# (joint) last author

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