Research Article: Artificial 64-Residue HIV-1 Enhancer-Binding Peptide Is a Potent Inhibitor of Viral Replication in HIV-1-Infected Cells

Date Published: September 19, 2011

Publisher: Hindawi Publishing Corporation

Author(s): Mouhssin Oufir, Leslie R. Bisset, Stefan R. K. Hoffmann, Gongda Xue, Stephan Klauser, Bianca Bergamaschi, Alain Gervaix, Jürg Böni, Jörg Schüpbach, Bernd Gutte.

http://doi.org/10.1155/2011/165871

Abstract

An artificial HIV-1 enhancer-binding peptide was extended by nine consecutive arginine residues at the C-terminus and by the nuclear localization signal of SV40 large T antigen at the N-terminus. The resulting synthetic 64-residue peptide was found to bind to the two enhancers of the HIV-1 long terminal repeat, cross the plasma membrane and the nuclear envelope of human cells, and suppress the HIV-1 enhancer-controlled expression of a green fluorescent protein reporter gene. Moreover, HIV-1 replication is inhibited by this peptide in HIV-1-infected CEM-GFP cells as revealed by HIV-1 p24 ELISA and real-time RT-PCR of HIV-1 RNA. Rapid uptake of this intracellular stable and inhibitory peptide into the cells implies that this peptide may have the potential to attenuate HIV-1 replication in vivo.

Partial Text

Treatment of HIV-1 infection has made considerable progress. Nevertheless, all current therapeutic approaches have been hampered by viral resistance mutations, undesired side effects, and high treatment cost [1].

We have shown earlier that a 42-residue peptide derived from the DNA-binding domain of bacteriophage 434 repressor bound specifically to the enhancer region of HIV-1 long terminal repeat and repressed the in vitro transcription of HIV-1 enhancer-containing plasmids [14]. In the present work we have demonstrated that this peptide was active in HIV-1-infected cells after it had been extended by a protein transduction domain to cross the plasma membrane and by a nuclear localization signal to enter the nucleus. The best results were obtained with peptide R64 (Figure 1(b)).

 

Source:

http://doi.org/10.1155/2011/165871

 

0 0 vote
Article Rating
Subscribe
Notify of
guest
0 Comments
Inline Feedbacks
View all comments