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Inhibition of Human Immunodeficiency Virus Type 1 Entry in Cells Expressing gp41-Derived Peptides.

Authors :
Egelhofer, Marc
Brandenburg, Gunda
Martinius, Holger
Schult-Dietrich, Patricia
Melikyan, Gregory
Kunert, Renate
Baum, Christopher
Choi, Ingrid
Alexandrov, Alexander
von Laer, Dorthee
Source :
Journal of Virology. Jan2004, Vol. 78 Issue 2, p568-575. 8p. 2 Diagrams, 1 Chart, 15 Graphs.
Publication Year :
2004

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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
0022538X
Volume :
78
Issue :
2
Database :
Academic Search Index
Journal :
Journal of Virology
Publication Type :
Academic Journal
Accession number :
12316933
Full Text :
https://doi.org/10.1128/JVI.78.2.568-575.2004