title: Leishmania infantum promastigotes reduce entry of HIV-1 into macrophages through a lipophosphoglycan-mediated disruption of lipid rafts.
abstract: Visceral leishmaniasis is now recognized as an opportunistic disease in patients infected with human immunodeficiency virus type 1 (HIV-1). We report here that Leishmania infantum promastigotes enhance HIV-1 replication in monocyte-derived macrophages (MDMs) at late time points in the virus growth curve but also that, surprisingly, a reduction in HIV-1 production is seen during the initial days after infection. This early effect is caused by a Leishmania-mediated inhibition of virus entry into MDMs through the action of lipophosphoglycan (LPG), the major promastigote surface glycolipid. The impact of LPG in the observed phenomenon was confirmed using LPG-defective lpg1-/- knockout mutant promastigotes. Our results suggest that the LPG-mediated effect results from the disruption of lipid rafts. Altogether, these findings suggest that the presence of Leishmania within the same cellular microenvironment leads to 2 opposite, time-dependent effects on HIV-1 replication. Leishmania and HIV-1 can thus establish complex interactions in their common natural host cells.
authors.affiliation: Centre de Recherche en Infectiologie, Centre Hospitalier de l'Université Laval, Université Laval, Québec (Québec), and 2INRS-Institut Armand-Frappier, Laval (Québec), Canada.
authors.forename: Ravendra
authors.initials: R
authors.lastname: Garg
authors.forename: Robert
authors.initials: R
authors.lastname: Lodge
authors.forename: Albert
authors.initials: A
authors.lastname: Descoteaux
authors.forename: Michel J
authors.initials: MJ
authors.lastname: Tremblay
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006028:Glycosphingolipids / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D018314:Leishmania infantum / Q000502:physiology*; D008264:Macrophages / Q000469:parasitology* / Q000821:virology*; D021962:Membrane Microdomains / Q000502:physiology*; D013997:Time Factors; D014779:Virus Replication
chemical_list: D006028:Glycosphingolipids; C008290:lipophosphonoglycan