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
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.