title: Galectin-1-specific inhibitors as a new class of compounds to treat HIV-1 infection.
abstract: Despite significant improvements, antiretroviral therapies against HIV-1 are plagued by a high frequency of therapeutic failures that have been associated with acquisition of drug resistance. We recently reported that HIV-1 exploits a host glycan binding protein, galectin-1, to increase its attachment to host cells, thereby increasing its overall infectivity in susceptible cells. This finding suggests that host molecules such as galectin-1 could reduce the expected efficiency of HIV-1 drugs targeting early steps of the replicative cycle, such as attachment and entry processes. Thus, new classes of drugs that would interfere with galectin-1/HIV-1 interactions could benefit the current antiretroviral therapy. To further explore this possibility, experiments were conducted to discover leading compounds showing specific inhibition of galectin-1 activity in a cellular model of HIV-1 infection. Three lactoside compounds were found to modestly inhibit the interaction of galectin-1 with primary human CD4(+) T cells. Interestingly, these same inhibitors reduced the galectin-1-mediated increase in HIV-1 attachment to target cells in a much more efficient manner. More important, the tested lactoside derivatives also significantly decreased the galectin-1-dependent enhancement of HIV-1 infection. These observations deserve further attention when considering that the development of new drugs to prevent and treat HIV-1 infection remains a priority.
authors: Glycobiology and Bioimaging Laboratory, Centre Hospitalier Universitaire de Québec-CHUL, and Faculté de Médecine, Université Laval, Quebec, Canada.
authors: Christian
authors: C
authors: St-Pierre
authors: Michel
authors: M
authors: Ouellet
authors: Denis
authors: D
authors: Giguère
authors: Reiko
authors: R
authors: Ohtake
authors: René
authors: R
authors: Roy
authors: Sachiko
authors: S
authors: Sato
authors: Michel J
authors: MJ
authors: Tremblay
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D024882:Drug Resistance, Viral; D037483:Galectin 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D017930:Genes, Reporter; D006027:Glycosides / Q000494:pharmacology* / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism; D057166:High-Throughput Screening Assays; D006801:Humans; D008156:Luciferases / Q000032:analysis; D061251:Primary Cell Culture; D011485:Protein Binding / Q000187:drug effects; D011991:Receptors, Virus / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D019562:Viral Load / Q000187:drug effects; D053585:Virus Attachment / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D037483:Galectin 1; D006027:Glycosides; D011991:Receptors, Virus; D011994:Recombinant Proteins; C008245:lactosides; D008156:Luciferases