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Antimicrobial Agents and Chemotherapy, November 2009, p. 4656-4666, Vol. 53, No. 11
0066-4804/09/$08.00+0     doi:10.1128/AAC.00117-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

LFA-1 Antagonists as Agents Limiting Human Immunodeficiency Virus Type 1 Infection and Transmission and Potentiating the Effect of the Fusion Inhibitor T-20{triangledown}

Mélanie R. Tardif,1 Caroline Gilbert,2 Sandra Thibault,1 Jean-François Fortin,3 and Michel J. Tremblay1*

Centre de Recherche en Infectiologie,1 Centre de Recherche en Rhumatologie et Immunologie, Centre Hospitalier de l'Université Laval, Faculté de Médecine, Université Laval, Québec, Canada,2 Boehringer-Ingelheim, Laval, Québec, Canada3

Received 27 January 2009/ Returned for modification 24 March 2009/ Accepted 20 August 2009

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.

* Corresponding author. Mailing address: Laboratoire d'Immuno-Rétrovirologie Humaine, Centre de Recherche en Infectiologie, RC709, 2705 Boul. Laurier, Québec (QC) G1V 4G2, Canada. Phone: (418) 654-2705. Fax: (418) 654-2212. E-mail: michel.j.tremblay{at}crchul.ulaval.ca

{triangledown} Published ahead of print on 31 August 2009.

Antimicrobial Agents and Chemotherapy, November 2009, p. 4656-4666, Vol. 53, No. 11
0066-4804/09/$08.00+0     doi:10.1128/AAC.00117-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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