Inhibition of human immunodeficiency virus type 1 entry in cells expressing gp41-derived peptides

M Egelhofer, G Brandenburg, H Martinius… - Journal of …, 2004 - Am Soc Microbiol
M Egelhofer, G Brandenburg, H Martinius, P Schult-Dietrich, G Melikyan, R Kunert, C Baum…
Journal of virology, 2004Am Soc Microbiol
As the limitations of antiretroviral drug therapy, such as toxicity and resistance, become
evident, interest in alternative therapeutic approaches for human immunodeficiency virus
(HIV) infection is growing. We developed the first gene therapeutic strategy targeting entry of
a broad range of HIV type 1 (HIV-1) variants. Infection was inhibited at the level of
membrane fusion by retroviral expression of a membrane-anchored peptide derived from
the second heptad repeat of the HIV-1 gp41 transmembrane glycoprotein. To achieve …
Abstract
As the limitations of antiretroviral drug therapy, such as toxicity and resistance, become evident, interest in alternative therapeutic approaches for human immunodeficiency virus (HIV) infection is growing. We developed the first gene therapeutic strategy targeting entry of a broad range of HIV type 1 (HIV-1) variants. Infection was inhibited at the level of membrane fusion by retroviral expression of a membrane-anchored peptide derived from the second heptad repeat of the HIV-1 gp41 transmembrane glycoprotein. To achieve maximal expression and antiviral activity, the peptide itself, the scaffold for presentation of the peptide on the cell surface, and the retroviral vector backbone were optimized. This optimized construct effectively inhibited virus replication in cell lines and primary blood lymphocytes. The membrane-anchored C-peptide was also shown to bind to free gp41 N peptides, suggesting that membrane-anchored antiviral C peptides have a mode of action similar to that of free gp41 C peptides. Preclinical toxicity and efficacy studies of this antiviral vector have been completed, and clinical trials are in preparation.
American Society for Microbiology