The V3 loop-mimicking pseudopeptide S[K psi(CH2N)PR]-TASP inhibits HIV infection in primary macrophage cultures

Citation
N. Seddiki et al., The V3 loop-mimicking pseudopeptide S[K psi(CH2N)PR]-TASP inhibits HIV infection in primary macrophage cultures, AIDS RES H, 15(4), 1999, pp. 381-390
Citations number
53
Categorie Soggetti
Immunology
Journal title
AIDS RESEARCH AND HUMAN RETROVIRUSES
ISSN journal
08892229 → ACNP
Volume
15
Issue
4
Year of publication
1999
Pages
381 - 390
Database
ISI
SICI code
0889-2229(19990301)15:4<381:TVLPSP>2.0.ZU;2-R
Abstract
The V3 loop-mimicking pseudopeptide 5[K psi(CH2N)PR]-TASP [psi(CH2N) repres enting a reduced peptide bond], which presents pentavalently the tripeptide K psi(CH2N)PR, is a potent inhibitor of HIV entry. By its capacity to bind specifically protein components on the cell surface, 5[K psi(CH2N)PR]-TASP blocks the attachment of virus particles to permissive CD4(+) cells. Here, the inhibitory effect of 5[K psi(CH2N)PR]-TASP was investigated in monocyt e-derived macrophages (MDMs) infected by the monocytotropic HIV-1(Ba-L) iso late. We show that 5[K psi(CH2N)PR]-TASP inhibits HIV-1(Ba-L) infection in a dose-dependent manner, with more than 90% inhibition at 2 mu M concentrat ion. On the other hand, the control 5[QPQ]-TASP construct and the monovalen t K psi(CH2N)PR tripeptide have no effect even at high concentrations, Unde r such experimental conditions, the biotin-labeled 5[K psi(CH2N)PR]-TASP, b ut not the K psi(CH2N)PR construct, binds specifically to the surface of MD Ms and forms a stable complex with the cell surface-expressed nucleolin, as has been demonstrated to be the case in peripheral blood mononuclear cells . Infection of MDMs by HIV-1(Ba-L) could also be inhibited by beta-chemokin es RANTES and MIP-1 beta. Interestingly, association of low concentrations of 5[K psi(CH2N)PR]-TASP and beta-chemokines results in a synergistic inhib itory effect on HIV infection compared with the effect observed with each r eagent alone. The inhibitory effect of 5[K psi(CH2N)PR]-TASP in primary mac rophage cultures point out its potential as an anti-HIV drug in cells, whic h are the natural viral targets.