600. Transduced Cells with Lentiviral Vector Expressing gp41-Derived c-Peptide Are Protected from HIV-1 Infection

Abstract

The HIV-1 envelope glycoprotein is composed of a complex between the surface subunit gp120, which binds to cellular receptors, and the transmembrane subunit gp41. Upon activation of the envelope glycoprotein by cellular receptors, gp41 undergoes conformational changes that mediate fusion of the viral and cellular membranes. The gp41 C-terminal heptad repeat region interacts with the N-terminal coiled-coil region to form a six-stranded core structure. As the limitations of anti-retroviral drug therapy, such as toxicity and resistance, interest in alternative therapeutic approaches for HIV-1 infection is growing. Based on HIV-1 glycoprotein, peptides derived from gp41 C-terminal heptad repeat region (C- peptides) are potent HIV-1 entry inhibitors by binding to gp41 N- terminal coiled-coil region. We hypothesize that expression of a membrane-bound C-peptides will confer HIV-1 resistance to target cells. Efficient gene delivery and stable expression of a membrane- bound C-peptides to target cells was accomplished using a self- inactivating lentiviral vector. Also, to achieve maximal expression and antiviral activity, the scaffold for presentation of the peptide on the cell surface was optimized. The HIV-1 entry inhibition effect by membrane-bound C-peptides can be mimicked by a fusion process between cells expressing the HIV envelope glycoprotein (gp160) and cells expressing both C-peptides together with human CD4 receptors. In this report, fusion events were monitored by the luciferase reporter system.