LFA-1 antagonists as agents limiting human immunodeficiency virus type 1 infection and transmission and potentiating the effect of the fusion inhibitor T-20.
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.
Tardif
Mélanie R
MR
Centre de Recherche en Infectiologie, Centre Hospitalier de l'Université Laval, Faculté de Médecine, Université Laval, Québec, Canada.
Gilbert
Caroline
C
Thibault
Sandra
S
Fortin
Jean-François
JF
Tremblay
Michel J
MJ
D019380:Anti-HIV Agents / Q000494:pharmacology*; D002460:Cell Line; D003713:Dendritic Cells / Q000502:physiology; D004357:Drug Synergism; D000077560:Enfuvirtide; D015700:HIV Envelope Protein gp41 / Q000494:pharmacology*; D023581:HIV Fusion Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D008148:Lovastatin / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D016169:Lymphocyte Function-Associated Antigen-1 / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology*; D010795:Phthalic Acids / Q000494:pharmacology*; D014771:Virion / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology
D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D016169:Lymphocyte Function-Associated Antigen-1; D010446:Peptide Fragments; D010795:Phthalic Acids; C546917:XVA 143; D015091:beta-Alanine; D018799:Intercellular Adhesion Molecule-1; D000077560:Enfuvirtide; D008148:Lovastatin