Inhibition of Human Immunodeficiency Virus Type 1 (HIV-1) Penetration into Target Cells by Synthetic Peptides Mimicking the N-Terminus of the HIV-1 Transmembrane Glycoprotein

Slepushkin, Vladimir; Kornilaeva, Galina V.; Andreev, S. M.; Sidorova, M. V.; Petrukhina, Anna; Matsevich, Gennady R.; Raduk, Svetlana V.; Grigoriev, V.; Makarova, Tatiana V.; Lukashov, Vladimir V.; Карамов, Э. В.

doi:10.1006/viro.1993.1260

Cited by 35 publications

(23 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, these short peptides were only effective at concentration of 1 mM (for the 6-aa long peptide (47) 11-aa long peptide (48)). In another study, Slepushkin et al (49) showed that a 22-aa long fusion peptide and its conjugate with bovine serum albumin inhibited HIV-1 infection at concentrations of 1 M. The effect of the peptide is certainly enhanced as its length increases. Here, we found that the 33-aa fusion peptides inhibited fusion at a concentration of 2 orders of magnitude lower than that reported for the 22-aa peptide (49).…”

Section: Discussionmentioning

confidence: 99%

“…In another study, Slepushkin et al (49) showed that a 22-aa long fusion peptide and its conjugate with bovine serum albumin inhibited HIV-1 infection at concentrations of 1 M. The effect of the peptide is certainly enhanced as its length increases. Here, we found that the 33-aa fusion peptides inhibited fusion at a concentration of 2 orders of magnitude lower than that reported for the 22-aa peptide (49). The fusion assay we used is based on the redistribution of fluorescent dyes about 2 h after incubation of the gp120-gp41-expressing cells with target cells and therefore measures initial events.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Fusion Peptides Derived from the HIV Type 1 Glycoprotein 41 Associate within Phospholipid Membranes and Inhibit Cell-Cell Fusion

Kliger

Aharoni

Rapaport

et al. 1997

Journal of Biological Chemistry

152

215

View full text Add to dashboard Cite

The fusion domain of human immunodeficiency virus (HIV-1) envelope glycoprotein (gp120-gp41) is a conserved hydrophobic region located at the N terminus of the transmembrane glycoprotein (gp41). A V2E mutant has been shown to dominantly interfere with wild-type envelope-mediated syncytium formation and virus infectivity. To understand this phenomenon, a 33-residue peptide (wild type, WT) identical to the N-terminal segment of gp41 and its V2E mutant were synthesized, fluorescently labeled, and characterized. Both peptides inhibited HIV-1 envelope-mediated cell-cell fusion and had similar ␣-helical content in membrane mimetic environments. Studies with fluorescently labeled peptide analogues revealed that both peptides have high affinity for phospholipid membranes, are susceptible to digestion by proteinase-K in their membrane-bound state, and tend to self-and coassemble in the membranes. In SDS-polyacrylamide gel electrophoresis the WT peptide formed dimers as well as higher order oligomers, whereas the V2E mutant only formed dimers. The WT, but not the V2E mutant, induced liposome aggregation, destabilization, and fusion. Moreover, the V2E mutant inhibited vesicle fusion induced by the WT peptide, probably by forming inactive heteroaggregates. These data form the basis for an explanation of the mechanism by which the gp41 V2E mutant inhibits HIV-1 infectivity in cells when co-expressed with WT gp41.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Fusion Peptides Derived from the HIV Type 1 Glycoprotein 41 Associate within Phospholipid Membranes and Inhibit Cell-Cell Fusion

Kliger

Aharoni

Rapaport

et al. 1997

Journal of Biological Chemistry

152

215

View full text Add to dashboard Cite

show abstract

“…48,53 Also of interest are the observations that selective modifications in synthetic N-terminal gp41 peptides reduced cytolytic and fusogenic activities, in parallel with the depressed syncytium-forming properties of the corresponding mutated full-length gp41. 36,41,43,48,50,51,53 Furthermore, addition of either N-terminal gp41 peptides 51,54 or anti-HIV agents 47,55-57 that bind to the gp41 terminus block virus-mediated fusion. Collectively, the above-described results suggest that critical fusogenic actions of HIV-1 are captured by synthetic N-terminal gp41 peptides.…”

Section: Introduction M Ost Models For Human Immunodeficiency Virus (mentioning

confidence: 99%

Membrane-Perturbing Domains of HIV Type 1 Glycoprotein 41

Mobley

Pilpa

Brown

et al. 2001

AIDS Research and Human Retroviruses

View full text Add to dashboard Cite

Structural and functional studies were performed to assess the membrane actions of peptides based on HIV-1 glycoprotein 41,000 (gp41). Previous site-directed mutagenesis of gp41 has shown that amino acid changes in either the N-terminal fusion or N-leucine zipper region depressed viral infection and syncytium formation, while modifications in the C-leucine zipper domain both increased and decreased HIV fusion. Here, synthetic peptides were prepared corresponding to the N-terminal fusion region (FP-I; gp41 residues 519-541), the nearby N-leucine zipper domain (DP-107; gp41 residues 560-597), and the C-leucine zipper domain (DP-178; gp41 residues 645-680). With erythrocytes, FP-I or DP-107 induced dose-dependent hemolysis and promoted cell aggregation; FP-I was more hemolytic than DP-107, but each was equally effective in aggregating cells. DP-178 produced neither hemolysis nor aggregation, but blocked either FP-I- or DP-107-induced hemolysis and aggregation. Combined with previous nuclear magnetic resonance and Fourier transform infrared spectroscopic results, circular dichroism (CD) spectroscopy showed that the alpha-helicity for these peptides in solution decreased in the order: DP-107 >> DP-178 > FP-I. CD analysis also indicated binding of DP-178 to either DP-107 or FP-I. Consequently, DP-178 may inhibit the membrane actions mediated by either FP-I or DP-107 through direct peptide interactions in solution. These peptide results suggest that the corresponding N-terminal fusion and N-leucine zipper regions participate in HIV infection, by promoting membrane perturbations underlying the merging of the viral envelope with the cell surface. Further, the C-leucine zipper domain in "prefusion" HIV may inhibit these membrane activities by interacting with the N-terminal fusion and N-leucine zipper domains in unactivated gp41. Last, exogenous DP-178 may bind to the N-terminal and N-leucine zipper domains of gp41 that become exposed on HIV stimulation, thereby preventing the fusogenic actions of these gp41 regions leading to infection.

show abstract

“…The inhibitory effect was sequence-specific and dosedependent. Longer HIV-1 FPs inhibited HIV-induced syncytium formation and antigen production in infected cells [56]. When peptide solubility was increased by a Cterminus conjugation to charged polymers an increase in inhibitory activity was found; 2) Coupled to partitioning, the FP attains a helical structure at the membraneinterface.…”

Section: Ii: Hiv-1 Fusion Inhibition By Targeting the Fusion Peptidementioning

confidence: 99%

Membrane-Transferring Regions of gp41 as Targets for HIV-1 Fusion Inhibition and Viral Neutralization

Huarte

Lorizate²,

Pérez‐Payá³

et al. 2011

CTMC

View full text Add to dashboard Cite

Abstract:The fusogenic function of HIV-1 gp41 transmembrane Env subunit relies on two different kinds of structural elements: i) a collapsible ectodomain structure (the hairpin or six-helix bundle) that opens and closes, and ii) two membrane-transferring regions (MTRs), the fusion peptide (FP) and the membrane-proximal external region (MPER), which ensure coupling of hairpin closure to apposition and fusion of cell and viral membranes. The isolation of naturally produced short peptides and neutralizing IgG-s, that interact with FP and MPER, respectively, and block viral infection, suggests that these conserved regions might represent useful targets for clinical intervention.Furthermore, MTR-derived peptides have been shown to be membrane-active. Here, it is discussed the potential use of these molecules and how the analysis of their membrane activity in vitro could contribute to the development of HIV fusion inhibitors and effective immunogens.2

show abstract

Inhibition of Human Immunodeficiency Virus Type 1 (HIV-1) Penetration into Target Cells by Synthetic Peptides Mimicking the N-Terminus of the HIV-1 Transmembrane Glycoprotein

Cited by 35 publications

References 0 publications

Fusion Peptides Derived from the HIV Type 1 Glycoprotein 41 Associate within Phospholipid Membranes and Inhibit Cell-Cell Fusion

Fusion Peptides Derived from the HIV Type 1 Glycoprotein 41 Associate within Phospholipid Membranes and Inhibit Cell-Cell Fusion

Membrane-Perturbing Domains of HIV Type 1 Glycoprotein 41

Membrane-Transferring Regions of gp41 as Targets for HIV-1 Fusion Inhibition and Viral Neutralization

Contact Info

Product

Resources

About