LFA-1 antagonists as agents limiting human immunodeficiency virus type 1 infection and transmission and potentiating the effect of the fusion inhibitor T-20.

Abstract

Adhesion molecules are known to play major roles in the initiation and stabilization of cell-to-cell contacts during the immunological response. Human immunodeficiency virus type 1 (HIV-1) exploits those interactions to facilitate infection and propagation processes. The primary objective of the present study was to investigate the ability of antagonists specific for lymphocyte function-associated antigen 1 (LFA-1) to diminish HIV-1 infection and transmission. We demonstrate here that LFA-1 antagonists can significantly reduce HIV-1 replication in primary human cells and virus propagation by affecting cell-to-cell interactions. Moreover, the inhibition of LFA-1-mediated adhesion events also potentiates the antiviral efficacy of the peptide fusion inhibitor T-20. Altogether, our data suggest that LFA-1 antagonists represent promising antiviral agents. Antiadhesion therapy could be considered a complementary strategy targeting cellular functions essential for HIV-1 spreading and against which the combined therapy currently used displays a limited efficacy.

• Authors: Mélanie R Tardif, Caroline Gilbert, Sandra Thibault, Jean-François Fortin, Michel J Tremblay
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 53 Issue 11 Pg. 4656-66 (Nov 2009) ISSN: 1098-6596 [Electronic] United States
• PMID: 19721069 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-HIV Agents
• HIV Envelope Protein gp41
• HIV Fusion Inhibitors
• Lymphocyte Function-Associated Antigen-1
• Peptide Fragments
• Phthalic Acids
• XVA 143
• beta-Alanine
• Intercellular Adhesion Molecule-1
• Enfuvirtide
• Lovastatin

Topics

• Anti-HIV Agents (pharmacology)
• Cell Line
• Dendritic Cells (physiology)
• Drug Synergism
• Enfuvirtide
• HIV Envelope Protein gp41 (pharmacology)
• HIV Fusion Inhibitors (pharmacology)
• HIV-1 (drug effects)
• Humans
• Intercellular Adhesion Molecule-1 (analysis)
• Lovastatin (pharmacology)
• Lymphocyte Activation (drug effects)
• Lymphocyte Function-Associated Antigen-1 (drug effects, physiology)
• Peptide Fragments (pharmacology)
• Phthalic Acids (pharmacology)
• Virion (drug effects)
• Virus Replication (drug effects)
• beta-Alanine (analogs & derivatives, pharmacology)