Novel Therapeutic Approach for Inhibition of HIV-1 Using Cell-Penetrating Peptide and Bacterial Toxins.

Terry D Connell,Marceline Egnin,Zainab Alwan,Toufic Nashar,Gregory Bernarda,Steven Samuels,Jessie Jaynes

doi:10.4172/2155-6113.1000737

Abstract

Despite advancements in our understanding of HIV-1 pathogenesis, critical virus components for immunity, vaccines trials, and drugs development, challenges remain in the fight against HIV-1. Of great importance is the inhibitory function of microbicidal cell penetrating peptides and bacterial toxins that interfere with production and neutralize infection of HIV-1 particles. We demonstrate that the neutralizing activity of a cationic 18 amino acids peptide, is similar to a broadly neutralizing human antibody, and inhibits production of two HIV-1 strains in human cell lines. Pretreatment of cells with bacterial toxins or toxoids derived from enterotoxigenic E. coli, boost subsequent activity of the peptide against HIV-1, to inhibit simultaneously production and infection. The synthetic peptide crosses the cell membrane into the cytoplasm and nucleus. In vitro analysis of a possible target for this peptide revealed specific binding to recombinant HIV-1 gag p24. This is the first demonstration of a synergy between bacterial toxins and a cell-penetrating peptide against HIV-1.

Highlights

A number of strategies have been designed to combat the development of AIDS in persons infected with the human immunodeficiency virus (HIV-1), including testing prototype vaccines and treatment with antiviral drugs
To examine whether the 18 amino acid peptide enters cells, human mammary epithelial cell line (HMEC) was incubated with the peptide, which was modified by biotinylation, and probed with streptavidin-Alexa
We investigated activity of a cationic peptide against two HIV-1 strains by using an indicator cell line that carries a stably integrated luciferase reporter gene under the control of the HIV-1 regulatory long terminal repeat element

Summary

Introduction

A number of strategies have been designed to combat the development of AIDS in persons infected with the human immunodeficiency virus (HIV-1), including testing prototype vaccines and treatment with antiviral drugs. The advantages gained from this approach would be the reduced ability of the HIV-1 virus to develop resistance due to the small size of the peptides, and interference with HIV-1 infection and replication by the peptide and toxins. Many peptides such as defensins, indolicidin, polyphemusin, and melittin, have activity against viruses including HIV-1, herpes simplex virus, influenza A virus, and vesicular stomatitis virus [8,9,10]. They inhibit protein subunits or protein-protein interactions due to their small size

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Results

Conclusion